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1.
Funct Integr Genomics ; 24(5): 154, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39223360

ABSTRACT

Proteus mirabilis is a gram-negative pathogen that caused significant opportunistic infections. In this study we aimed to identify antimicrobial resistance (AMR) genes and virulence determinants in two pan-drug resistant isolate "Bacteria_11" and "Bacteria_27" using whole genome sequencing. Proteus mirabilis "Bacteria_11" and "Bacteria_27" were isolated from two different hospitalized patients in Egypt. Antimicrobial susceptibility determined using Vitek 2 system, then whole genome sequencing (WGS) using MinION nanopore sequencing was done. Antimicrobial resistant genes and virulence determinants were identified using ResFinder, CADR AMR database, Abricate tool and VF analyzer were used respectively. Multiple sequence alignment was performed using MAFFT and FastTree, respectively. All genes were present within bacterial chromosome and no plasmid was detected. "Bacteria_11" and "Bacteria_27" had sizes of approximately 4,128,657 bp and 4,120,646 bp respectively, with GC content of 39.15% and 39.09%. "Bacteria_11" and "Bacteria_27" harbored 43 and 42 antimicrobial resistance genes respectively with different resistance mechanisms, and up to 55 and 59 virulence genes respectively. Different resistance mechanisms were identified: antibiotic inactivation, antibiotic efflux, antibiotic target replacement, and antibiotic target change. We identified several genes associated with aminoglycoside resistance, sulfonamide resistance. trimethoprim resistance tetracycline resistance proteins. Also, those responsible for chloramphenicol resistance. For beta-lactam resistance, only blaVEB and blaCMY-2 genes were detected. Genome analysis revealed several virulence factors contribution in isolates pathogenicity and bacterial adaptation. As well as numerous typical secretion systems (TSSs) were present in the two isolates, including T6SS and T3SS. Whole genome sequencing of both isolates identify their genetic context of antimicrobial resistant genes and virulence determinants. This genomic analysis offers detailed representation of resistant mechanisms. Also, it clarifies P. mirabilis ability to acquire resistance and highlights the emergence of extensive drug resistant (XDR) and pan-drug resistant (PDR) strains. This may help in choosing the most appropriate antibiotic treatment and limiting broad spectrum antibiotic use.


Subject(s)
Drug Resistance, Multiple, Bacterial , Proteus mirabilis , Virulence Factors , Proteus mirabilis/genetics , Proteus mirabilis/pathogenicity , Proteus mirabilis/drug effects , Proteus mirabilis/isolation & purification , Drug Resistance, Multiple, Bacterial/genetics , Virulence Factors/genetics , Genome, Bacterial , Humans , Anti-Bacterial Agents/pharmacology , Whole Genome Sequencing , Virulence/genetics , Microbial Sensitivity Tests , Proteus Infections/microbiology , Proteus Infections/drug therapy
2.
J Microbiol Methods ; 224: 107008, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39103095

ABSTRACT

Proteus mirabilis is a predominant species in cases of food poisoning associated with meat products and is also an opportunistic pathogen causing numerous infections in humans. This study aimed to differentiate P. mirabilis isolates using intergenic region polymorphism analysis (IRPA). The IRPA typing scheme was developed to amplify polymorphic fragments in intergenic regions (IGRs). The presence, absence, or size change of amplified products were identified and utilized as genetic markers for rapid differentiation of strains. A total of 75 P. mirabilis isolates were isolated from 63 fresh poultry and pork samples were subtyped using the IRPA and ERIC-PCR methods, and their antibiotic resistance profiles were tested. The majority of P. mirabilis isolates showed resistance to tetracycline (85.3%), doxycycline (93.3%), chloramphenicol (82.7%), streptomycin (92.0%), spectinomycin (80.0%), trimethoprim (97.3%); trimethoprim-sulfalleth (82.7%), and erythromycin (100.0%). In contrast, resistance rates to ceftriaxon, cefoxitin, cefepime, and cefotaxim were lower at only 17.3%, 5.3%, 6.7%, and 13.3%, respectively, among P. mirabilis isolates. Eleven loci were selected for analysis of the genetic diversity of 75 P. mirabilis isolates. A combination of 4 loci was determined as the optimal combination. The results compared to those obtained using ERIC-PCR for the same isolates. The Simpson's index of diversity was 0.999 for IRPA and 0.923 for ERIC-PCR, indicating that IRPA has a higher discriminatory power than ERIC-PCR. The concordance between IRPA and ERIC-PCR methods was low, primarily because IRPA classified isolates from the same ERIC cluster into separate clusters due to its high resolution. The IRPA method presented in this study offers a rapid, simple, reproducible, and economical approach for genotyping P. mirabilis.


Subject(s)
Anti-Bacterial Agents , DNA, Intergenic , Polymerase Chain Reaction , Proteus mirabilis , Proteus mirabilis/genetics , Proteus mirabilis/drug effects , Proteus mirabilis/isolation & purification , Polymerase Chain Reaction/methods , Animals , Anti-Bacterial Agents/pharmacology , DNA, Intergenic/genetics , Swine , Polymorphism, Genetic , Poultry/microbiology , Genotyping Techniques/methods , Genotype , Microbial Sensitivity Tests , DNA, Bacterial/genetics , Proteus Infections/microbiology , Drug Resistance, Bacterial/genetics , Bacterial Typing Techniques/methods
3.
BMC Microbiol ; 24(1): 312, 2024 Aug 24.
Article in English | MEDLINE | ID: mdl-39182027

ABSTRACT

BACKGROUND: More than a century has passed since it was discovered that many bacteria produce indole, but research into the actual biological roles of this molecule is just now beginning. The influence of indole on bacterial virulence was extensively investigated in indole-producing bacteria like Escherichia coli. To gain a deeper comprehension of its functional role, this study investigated how indole at concentrations of 0.5-1.0 mM found in the supernatant of Escherichia coli stationary phase culture was able to alter the virulence of non-indole-producing bacteria, such as Pseudomonas aeruginosa, Proteus mirabilis, and Klebsiella pneumoniae, which are naturally exposed to indole in mixed infections with Escherichia coli. RESULTS: Biofilm formation, antimicrobial susceptibility, and efflux pump activity were the three phenotypic tests that were assessed. Indole was found to influence antibiotic susceptibly of Pseudomonas aeruginosa, Proteus mirabilis and Klebsiella pneumoniae to ciprofloxacin, imipenem, ceftriaxone, ceftazidime, and amikacin through significant reduction in MIC with fold change ranged from 4 to 16. Biofilm production was partially abrogated in both 32/45 Pseudomonas aeruginosa and all eight Proteus mirabilis, while induced biofilm production was observed in 30/40 Klebsiella pneumoniae. Moreover, acrAB and oqxAB, which encode four genes responsible for resistance-nodulation-division multidrug efflux pumps in five isolates of Klebsiella pneumoniae were investigated genotypically using quantitative real-time (qRT)-PCR. This revealed that all four genes exhibited reduced expression indicated by 2^-ΔΔCT < 1 in indole-treated isolates compared to control group. CONCLUSION: The outcomes of qRT-PCR investigation of efflux pump expression have established a novel clear correlation of the molecular mechanism that lies beneath the influence of indole on bacterial antibiotic tolerance. This research provides novel perspectives on the various mechanisms and diverse biological functions of indole signaling and how it impacts the pathogenicity of non-indole-producing bacteria.


Subject(s)
Anti-Bacterial Agents , Biofilms , Escherichia coli , Indoles , Klebsiella pneumoniae , Microbial Sensitivity Tests , Pseudomonas aeruginosa , Klebsiella pneumoniae/genetics , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/metabolism , Biofilms/growth & development , Biofilms/drug effects , Indoles/metabolism , Indoles/pharmacology , Escherichia coli/genetics , Escherichia coli/drug effects , Escherichia coli/metabolism , Anti-Bacterial Agents/pharmacology , Pseudomonas aeruginosa/genetics , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/metabolism , Gene Expression Regulation, Bacterial/drug effects , Down-Regulation , Proteus mirabilis/genetics , Proteus mirabilis/drug effects , Proteus mirabilis/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Membrane Transport Proteins/genetics , Membrane Transport Proteins/metabolism , Virulence/genetics , Escherichia coli Proteins/genetics , Escherichia coli Proteins/metabolism
4.
J Appl Microbiol ; 135(7)2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38991984

ABSTRACT

AIMS: We aimed to identify mechanisms underlying the tolerance of Proteus mirabilis-a common cause of catheter associated urinary tract infection-to the clinically used biocides chlorhexidine (CHD) and octenidine (OCT). METHODS AND RESULTS: We adapted three clinical isolates to grow at concentrations of 512 µg ml-1 CHD and 128 µg ml-1 OCT. Genetic characterization and complementation studies revealed mutations inactivating the smvR repressor and increasing smvA efflux expression were associated with adaptation to both biocides. Mutations in mipA (encoding the MltA interacting protein) were less prevalent than smvR mutations and only identified in CHD adapted populations. Mutations in the rppA response regulator were exclusive to one adapted isolate and were linked with reduced polymyxin B susceptibility and a predicted gain of function after biocide adaptation. Biocide adaptation had no impact on crystalline biofilm formation. CONCLUSIONS: SmvR inactivation is a key mechanism in both CHD and OCT tolerance. MipA inactivation alone confers moderate protection against CHD, and rppA showed no direct role in either CHD or OCT susceptibility.


Subject(s)
Chlorhexidine , Imines , Proteus mirabilis , Pyridines , Proteus mirabilis/drug effects , Proteus mirabilis/genetics , Proteus mirabilis/physiology , Chlorhexidine/pharmacology , Imines/pharmacology , Pyridines/pharmacology , Microbial Sensitivity Tests , Humans , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Biofilms/drug effects , Biofilms/growth & development , Proteus Infections/microbiology , Mutation , Drug Resistance, Bacterial/genetics , Anti-Infective Agents, Local/pharmacology , Disinfectants/pharmacology , Catheter-Related Infections/microbiology , Urinary Tract Infections/microbiology
5.
Sci Rep ; 14(1): 16362, 2024 07 16.
Article in English | MEDLINE | ID: mdl-39014066

ABSTRACT

Chronic Otitis Media (COM) is defined as long term inflammation and colonization with pathogenic bacteria due to a defect or retraction of the tympanic membrane. Surgical interventions are often augmented by antibiotic resistance development and therefore, off-label treatment using the natural drug 1,8-Cineol was carried out. All COM patients underwent antibiotic therapy and middle ear surgery and developed antibiotic resistances. Microbiological investigations from the auditory canal and stool samples were performed in correlation with the clinical course. Therapy of COM patients with 1,8-Cineol revealed a clear reduction of inflammatory microbes P. aeruginosa and Proteus mirabilis in ear samples as well as intestinal Prevotella copri, which was associated with an improved clinical outcome in certain individuals. The present off-label study revealed manifold anti-inflammatory effects of the natural monoterpene 1,8-Cineol in Otitis media patients. A better understanding of the underlying mechanisms will improve the current treatment options and possible forms of application of this natural drug.


Subject(s)
Otitis Media , Otitis Media/microbiology , Otitis Media/drug therapy , Humans , Female , Male , Middle Aged , Adult , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Proteus mirabilis/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Microbiota/drug effects , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/isolation & purification , Aged
6.
BMC Complement Med Ther ; 24(1): 256, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982425

ABSTRACT

BACKGROUND: One of the most widely used medicinal plants in Iranian traditional medicine, Rosa × damascena Herrm. (mohammadi flower) that the people of Kashan use as a sedative and to treat nervous diseases and constipation. In this research, the yield, chemical composition and antimicrobial activity of the essential oil of this plant were evaluated for the first time from Azaran region, Kashan. METHODS: The essential oil was extracted by means of hydrodistillation (Clevenger), and its chemical compounds were identified and determined by GC/MS. The antimicrobial activity of the essential oil was determined by the diffusion method in agar, the minimum growth inhibitory concentration (MIC) and the minimum concentration capable of killing bacterial/fungal microorganisms (MBC/MFC). RESULTS: The results showed that the yield of essential oil was 0.1586 ± 0.0331% (w/w). Based on the results of the chemical composition analysis of R. x damascena essential oil, 19 different compounds (98.96%) were identified. The dominant and main components of the essential oil were oleic acid (48.08%), palmitic acid (15.44%), stearic acid (10.17%), citronellol (7.37%) and nonadecane (3.70%). Based on the results of diffusion in agar, the highest zone of inhibition against Candida albicans (ATCC 10231) was ~ 9.5 mm. The strongest inhibitory activity of R. x damascena essential oil against Gram-negative Proteus mirabilis (ATCC 43071) was with the diameter of the inhibition zone (~ 9 mm), which was equal to the strength of rifampin (~ 9 mm). CONCLUSION: Therefore, this essential oil is a promising natural option rich in fatty acids, which can be a potential for the production of natural antimicrobials against infectious diseases, especially urinary tract infections.


Subject(s)
Microbial Sensitivity Tests , Oils, Volatile , Proteus mirabilis , Rosa , Proteus mirabilis/drug effects , Oils, Volatile/pharmacology , Oils, Volatile/chemistry , Iran , Rosa/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Fatty Acids, Unsaturated/pharmacology , Fatty Acids, Unsaturated/chemistry
7.
Pak J Biol Sci ; 27(5): 268-275, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38840467

ABSTRACT

<b>Background and Objective:</b> Urinary tract infections from the use of an indwelling urinary catheter are one of the most common infections caused by <i>Proteus mirabilis</i>. Due to their biofilm-producing capacity and the increasing antimicrobial resistance in this microorganism, this study aimed to determine the prevalence, biofilm-producing capacity, antimicrobial resistance patterns, multidrug resistance and plasmid mediated resistance of the recovered isolates. <b>Materials and Methods:</b> A total of 50 urinary samples were collected from May to August, 2018 from patients on indwelling urinary catheters. Using routine microbiological and biochemical methods, 37 <i>P. mirabilis</i> were isolated. Biofilm forming capability was determined among the isolates using the tube method while antimicrobial susceptibility and plasmid curing were also performed. <b>Results:</b> All isolates were biofilm producers with 17(46%) being moderate producers while 20(54%) were strong biofilm formers. The study isolates exhibited a high resistance rate to empiric antibiotics, including ceftazidime (75.8%), cefuroxime (54.5%), ampicillin (69.7%) and amoxicillin-clavulanic acid (51.5%). Low resistance was seen in the fluoroquinolones, gentamicin and nitrofurantoin. Plasmid curing experiment revealed that most isolates lost their resistance indicating that resistance was borne on plasmids. Plasmid carriage is likely the reason for the high MDR rate of 56.8% observed. <b>Conclusion:</b> These findings necessitate the provision of infection control programs which will guide and implement policies.


Subject(s)
Anti-Bacterial Agents , Biofilms , Catheters, Indwelling , Microbial Sensitivity Tests , Proteus mirabilis , Biofilms/drug effects , Biofilms/growth & development , Proteus mirabilis/drug effects , Proteus mirabilis/genetics , Proteus mirabilis/isolation & purification , Catheters, Indwelling/microbiology , Catheters, Indwelling/adverse effects , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Urinary Tract Infections/microbiology , Urinary Tract Infections/drug therapy , Urinary Tract Infections/diagnosis , Plasmids/genetics , Urinary Catheters/microbiology , Urinary Catheters/adverse effects , Drug Resistance, Bacterial , Proteus Infections/microbiology , Proteus Infections/drug therapy , Catheter-Related Infections/microbiology , Catheter-Related Infections/diagnosis , Catheter-Related Infections/drug therapy , Female , Male , Drug Resistance, Multiple, Bacterial/genetics
8.
BMC Microbiol ; 24(1): 216, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38890647

ABSTRACT

OBJECTIVE: This study aims to conduct an in-depth genomic analysis of a carbapenem-resistant Proteus mirabilis strain to uncover the distribution and mechanisms of its resistance genes. METHODS: The research primarily utilized whole-genome sequencing to analyze the genome of the Proteus mirabilis strain. Additionally, antibiotic susceptibility tests were conducted to evaluate the strain's sensitivity to various antibiotics, and related case information was collected to analyze the clinical distribution characteristics of the resistant strain. RESULTS: Study on bacterial strain WF3430 from a tetanus and pneumonia patient reveals resistance to multiple antibiotics due to extensive use. Whole-genome sequencing exposes a 4,045,480 bp chromosome carrying 29 antibiotic resistance genes. Two multidrug-resistant (MDR) gene regions, resembling Tn6577 and Tn6589, were identified (MDR Region 1: 64.83 Kb, MDR Region 2: 85.64 Kbp). These regions, consist of integrative and conjugative elements (ICE) structures, highlight the intricate multidrug resistance in clinical settings. CONCLUSION: This study found that a CR-PMI strain exhibits a unique mechanism for acquiring antimicrobial resistance genes, such as blaNDM-1, located on the chromosome instead of plasmids. According to the results, there is increasing complexity in the mechanisms of horizontal transmission of resistance, necessitating a comprehensive understanding and implementation of targeted control measures in both hospital and community settings.


Subject(s)
Anti-Bacterial Agents , Bacterial Proteins , Drug Resistance, Multiple, Bacterial , Microbial Sensitivity Tests , Proteus Infections , Proteus mirabilis , Whole Genome Sequencing , beta-Lactamases , Proteus mirabilis/genetics , Proteus mirabilis/drug effects , Proteus mirabilis/enzymology , Proteus mirabilis/isolation & purification , beta-Lactamases/genetics , Humans , Drug Resistance, Multiple, Bacterial/genetics , Anti-Bacterial Agents/pharmacology , Proteus Infections/microbiology , Bacterial Proteins/genetics , Chromosomes, Bacterial/genetics , Genome, Bacterial/genetics , Carbapenems/pharmacology
9.
Ann Clin Microbiol Antimicrob ; 23(1): 46, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38790053

ABSTRACT

BACKGROUND: Proteus mirabilis is an opportunistic pathogen that has been held responsible for numerous nosocomial and community-acquired infections which are difficult to be controlled because of its diverse antimicrobial resistance mechanisms. METHODS: Antimicrobial susceptibility patterns of P. mirabilis isolates collected from different clinical sources in Mansoura University Hospitals, Egypt was determined. Moreover, the underlying resistance mechanisms and genetic relatedness between isolates were investigated. RESULTS: Antimicrobial susceptibility testing indicated elevated levels of resistance to different classes of antimicrobials among the tested P. mirabilis clinical isolates (n = 66). ERIC-PCR showed great diversity among the tested isolates. Six isolates (9.1%) were XDR while all the remaining isolates were MDR. ESBLs and AmpCs were detected in 57.6% and 21.2% of the isolates, respectively, where blaTEM, blaSHV, blaCTX-M, blaCIT-M and blaAmpC were detected. Carbapenemases and MBLs were detected in 10.6 and 9.1% of the isolates, respectively, where blaOXA-48 and blaNDM-1 genes were detected. Quinolone resistant isolates (75.8%) harbored acc(6')-Ib-cr, qnrD, qnrA, and qnrS genes. Resistance to aminoglycosides, trimethoprim-sulfamethoxazole and chloramphenicol exceeded 80%. Fosfomycin was the most active drug against the tested isolates as only 22.7% were resistant. Class I or II integrons were detected in 86.4% of the isolates. Among class I integron positive isolates, four different gene cassette arrays (dfrA17- aadA5, aadB-aadA2, aadA2-lnuF, and dfrA14-arr-3-blaOXA-10-aadA15) and two gene cassettes (dfrA7 and aadA1) were detected. While class II integron positive isolates carried four different gene cassette arrays (dfrA1-sat1-aadA1, estXVr-sat2-aadA1, lnuF- dfrA1-aadA1, and dfrA1-sat2). CONCLUSION: P. Mirabilis ability to acquire resistance determinants via integrons may be held responsible for the elevated rates of antimicrobial resistance and emergence of XDR or even PDR strains limiting the available therapeutic options for management of infections caused by those strains.


Subject(s)
Anti-Bacterial Agents , Drug Resistance, Multiple, Bacterial , Microbial Sensitivity Tests , Proteus Infections , Proteus mirabilis , Egypt/epidemiology , Humans , Proteus mirabilis/genetics , Proteus mirabilis/drug effects , Proteus mirabilis/isolation & purification , Drug Resistance, Multiple, Bacterial/genetics , Proteus Infections/microbiology , Proteus Infections/epidemiology , Anti-Bacterial Agents/pharmacology , Prevalence , beta-Lactamases/genetics , Integrons/genetics , Bacterial Proteins/genetics , Cross Infection/microbiology , Cross Infection/epidemiology , Male
10.
J Mater Chem B ; 12(23): 5711-5721, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38758163

ABSTRACT

The presence of a variety of bacteria is an inevitable/indispensable part of human life. In particular, for patients, the existence and spreading of bacteria lead to prolonged treatment period with many more complications. The widespread use of urinary catheters is one of the main causes for the prevalence of infections. The necessity of long-term use of indwelling catheters is unavoidable in terms of the development of bacteriuria and blockage. As is known, since a permanent solution to this problem has not yet been found, research and development activities continue actively. Herein, polyethylene glycol (PEG)-like thin films were synthesized by a custom designed plasma enhanced chemical vapor deposition (PE-CVD) method and the long-term effect of antifouling properties of PEG-like coated catheters was investigated against Escherichia coli and Proteus mirabilis. The contact angle measurements have revealed the increase of wettability with the increase of plasma exposure time. The antifouling activity of surface-coated catheters was analyzed against the Gram-negative/positive bacteria over a long-term period (up to 30 days). The results revealed that PE-CVD coated PEG-like thin films are highly capable of eliminating bacterial attachment on surfaces with relatively reduced protein attachment without having any toxic effect. Previous statements were supported with SEM, XPS, FTIR spectroscopy, and contact angle analysis.


Subject(s)
Escherichia coli , Polyethylene Glycols , Proteus mirabilis , Surface Properties , Urinary Catheters , Urinary Catheters/microbiology , Escherichia coli/drug effects , Proteus mirabilis/drug effects , Polyethylene Glycols/chemistry , Bacterial Adhesion/drug effects , Biofouling/prevention & control , Humans , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology
11.
Ann Clin Microbiol Antimicrob ; 23(1): 48, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802894

ABSTRACT

BACKGROUND: Proteus mirabilis is a significant nosocomial pathogen that is frequently associated with a wide range of infections, necessitating heightened attention to mitigate potential health risks. Hence, this study was performed to investigate the impact of sub-minimum inhibitory concentrations (MICs) of ciprofloxacin (CIP) on Proteus mirabilis clinical isolates. METHODS: The sub-MICs of CIP were selected using the growth curve approach. The untreated and treated isolates with sub-MICs of CIP were assessed for their biofilm development, motilities on agar, and other virulence factors. The cell morphology of untreated and treated isolates with sub-MIC of CIP was explored using electron microscope. Moreover, the expression levels of the virulence genes in isolates were measured using quantitative real-time PCR. RESULTS: Data revealed that sub-MICs of CIP significantly (p < 0.05), in a concentration-dependent manner, inhibited biofilm formation and other virulence factors in the selected isolates. Electron microscope analysis showed cell enlargement and various abnormalities in the cell wall and membrane integrity. CONCLUSION: Sub-MICs of CIP exhibited inhibition of virulence and alterations in morphological integrity against P. mirabilis isolates.


Subject(s)
Anti-Bacterial Agents , Biofilms , Ciprofloxacin , Microbial Sensitivity Tests , Proteus Infections , Proteus mirabilis , Virulence Factors , Proteus mirabilis/drug effects , Proteus mirabilis/genetics , Ciprofloxacin/pharmacology , Biofilms/drug effects , Biofilms/growth & development , Humans , Anti-Bacterial Agents/pharmacology , Proteus Infections/microbiology , Virulence Factors/genetics , Virulence/drug effects
12.
Emerg Microbes Infect ; 13(1): 2353310, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38712879

ABSTRACT

OXA-48-like enzymes represent the most frequently detected carbapenemases in Enterobacterales in Western Europe, North Africa and the Middle East. In contrast to other species, the presence of OXA-48-like in Proteus mirabilis leads to an unusually susceptible phenotype with low MICs for carbapenems and piperacillin-tazobactam, which is easily missed in the diagnostic laboratory. So far, there is little data available on the genetic environments of the corresponding genes, blaOXA-48-like, in P. mirabilis. In this study susceptibility phenotypes and genomic data of 13 OXA-48-like-producing P. mirabilis were investigated (OXA-48, n = 9; OXA-181, n = 3; OXA-162, n = 1). Ten isolates were susceptible to meropenem and ertapenem and three isolates were susceptible to piperacillin-tazobactam. The gene blaOXA-48 was chromosomally located in 7/9 isolates. Thereof, in three isolates blaOXA-48 was inserted into a P. mirabilis genomic island. Of the three isolates harbouring blaOXA-181 one was located on an IncX3 plasmid and two were located on a novel MOBF plasmid, pOXA-P12, within the new transposon Tn7713. In 5/6 isolates with plasmidic location of blaOXA-48-like, the plasmids could conjugate to E. coli recipients in vitro. Vice versa, blaOXA-48-carrying plasmids could conjugate from other Enterobacterales into a P. mirabilis recipient. These data show a high diversity of blaOXA-48-like genetic environments compared to other Enterobacterales, where genetic environments are quite homogenous. Given the difficult-to-detect phenotype of OXA-48-like-producing P. mirabilis and the location of blaOXA-48-like on mobile genetic elements, it is likely that OXA-48-like-producing P. mirabilis can disseminate, escape most surveillance systems, and contribute to a hidden spread of OXA-48-like.


Subject(s)
Anti-Bacterial Agents , Bacterial Proteins , Microbial Sensitivity Tests , Proteus Infections , Proteus mirabilis , beta-Lactamases , Proteus mirabilis/genetics , Proteus mirabilis/enzymology , Proteus mirabilis/isolation & purification , Proteus mirabilis/drug effects , beta-Lactamases/genetics , beta-Lactamases/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Anti-Bacterial Agents/pharmacology , Humans , Proteus Infections/microbiology , Plasmids/genetics , Genomic Islands , Carbapenems/pharmacology
13.
BJU Int ; 134(1): 72-80, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38459675

ABSTRACT

OBJECTIVES: To investigate the ability of propolis-coated ureteric stents to solve complications, especially urinary tract infections (UTIs) and crusting, in patients with long-term indwelling ureteric stents through antimicrobial and anti-calculus activities. MATERIALS AND METHODS: Polyurethane (PU) ureteric stents were immersed in the ethanol extract of propolis (EEP), a well-known antimicrobial honeybee product, and subjected to chemical, hydrophilic, and seismic tests. The antimicrobial activity of the EEP coating was then examined by in vitro investigation. Proteus mirabilis infection was induced in rats within uncoated and EEP-coated groups, and the infection, stone formation, and inflammation were monitored at various time points. RESULTS: The characterisation results showed that the hydrophilicity and stability of the EEP surface improved. In vitro tests revealed that the EEP coating was biocompatible, could eliminate >90% of bacteria biofilms attached to the stent and could maintain bacteriostatic properties for up to 3 months. The in vivo experiment revealed that the EEP-coating significantly reduced the amount of bacteria, stones, and salt deposits on the surface of the ureteric stents and decreased inflammation in the host tissue. CONCLUSIONS: Compared with clinically used PU stents, EEP-coated ureteric stents could better mitigate infections and prevent encrustation. Thus, this study demonstrated that propolis is a promising natural dressing material for ureteric stents.


Subject(s)
Anti-Bacterial Agents , Coated Materials, Biocompatible , Propolis , Stents , Ureter , Animals , Rats , Propolis/pharmacology , Anti-Bacterial Agents/pharmacology , Coated Materials, Biocompatible/pharmacology , Proteus mirabilis/drug effects , Male , Urinary Tract Infections/prevention & control , Rats, Sprague-Dawley , Biofilms/drug effects , Proteus Infections/prevention & control , Polyurethanes
14.
J Microbiol Immunol Infect ; 57(3): 385-395, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38453541

ABSTRACT

BACKGROUND: Copper plays a role in urinary tract infection (UTI) and urinary copper content is increased during Proteus mirabilis UTI. We therefore investigated the effect of copper on uropathogenic P. mirabilis and the underlying mechanisms, focusing on the virulence associated aspects. METHODS: Mouse colonization, swarming/swimming assays, measurement of cell length, flagellin level and urease activity, adhesion/invasion assay, biofilm formation, killing by macrophages, oxidative stress susceptibility, OMPs analysis, determination of MICs and persister cell formation, RT-PCR and transcriptional reporter assay were performed. RESULTS: We found that copper-supplemented mice were more resistant to be colonized in the urinary tract, together with decreased swarming/swimming, ureases activity, expression of type VI secretion system and adhesion/invasion to urothelial cells and increased killing by macrophages of P. mirabilis at a sublethal copper level. However, bacterial biofilm formation and resistance to oxidative stress were enhanced under the same copper level. Of note, the presence of copper led to increased ciprofloxacin MIC and more persister cell formation against ampicillin. In addition, the presence of copper altered the outer membrane protein profile and triggered expression of RcsB response regulator. For the first time, we unveiled the pleiotropic effects of copper on uropathogenic P. mirabilis, especially for induction of bacterial two-component signaling system regulating fitness and virulence. CONCLUSION: The finding of copper-mediated virulence and fitness reinforced the importance of copper for prevention and therapeutic interventions against P. mirabilis infections. As such, this study could facilitate the copper-based strategies against UTI by P. mirabilis.


Subject(s)
Biofilms , Copper , Microbial Sensitivity Tests , Proteus Infections , Proteus mirabilis , Urinary Tract Infections , Proteus mirabilis/drug effects , Proteus mirabilis/pathogenicity , Proteus mirabilis/physiology , Proteus mirabilis/genetics , Animals , Urinary Tract Infections/microbiology , Copper/pharmacology , Mice , Virulence , Biofilms/drug effects , Biofilms/growth & development , Proteus Infections/microbiology , Female , Phenotype , Anti-Bacterial Agents/pharmacology , Oxidative Stress/drug effects , Macrophages/microbiology , Bacterial Adhesion/drug effects , Bacterial Proteins/genetics , Bacterial Proteins/metabolism
15.
Sci Rep ; 12(1): 13992, 2022 08 17.
Article in English | MEDLINE | ID: mdl-35978046

ABSTRACT

Proteus mirabilis (P. mirabilis) is a frequent cause of catheter-associated urinary tract infections. This study aims to investigate the anti-infective effect of Alhagi maurorum extract (AME), the traditional medicinal plant in the middle east, on the biofilm-forming P. mirabilis isolates. Hydroalcoholic extract and oil of A. maurorum were characterized by HPLC and GC-MS. The antiproliferative, anti-biofilm, and bactericidal activity of AME at various concentrations were assessed by turbidity, crystal violet binding, and agar well diffusion assays, respectively. The AME's effect on adhesion and quorum sensing (QS) were investigated by in vitro adhesion assay on cell culture and agar overlay assay using Janthinobacterium lividum (ATCC 12472) as a biosensor strain. In addition, the expression level of selected genes involved in QS and biofilm regulation were determined by quantitative Real-Time PCR. Furthermore, the bladder phantom model was created to evaluate the assays and investigate the catheter's calcium deposition. The most effective chemical compounds found in AME were tamarixetin, quercetin, and trans-anethole. Although AME did not inhibit swarming motility, it reduced biofilm production and exerted a concentration-dependent anti-adhesive and anti-QS activity against P. mirabilis. AME also downregulated the expression level of selected genes involved in biofilm formation and QS. This study showed that AME as a natural compound reduced biofilm formation of P. mirabilis by targeting virulence factor genes, quorum sensing, and other strategies that include preventing the adhesion of P. mirabilis to the cells. The results suggest that A. maurorum extract might have the potential to be considered for preventing UTIs caused by P. mirabilis.


Subject(s)
Biofilms , Fabaceae , Plant Extracts , Plants, Medicinal , Proteus mirabilis , Quorum Sensing , Agar , Anti-Bacterial Agents/pharmacology , Bacterial Adhesion/drug effects , Biofilms/drug effects , Biofilms/growth & development , Catheters/adverse effects , Catheters/microbiology , Fabaceae/chemistry , Humans , Phytotherapy , Plant Extracts/pharmacology , Plants, Medicinal/chemistry , Proteus mirabilis/drug effects , Proteus mirabilis/genetics , Proteus mirabilis/pathogenicity , Proteus mirabilis/physiology , Quorum Sensing/drug effects , Quorum Sensing/genetics , Urinary Tract Infections/microbiology , Virulence/drug effects , Virulence/genetics
16.
Molecules ; 27(3)2022 Feb 06.
Article in English | MEDLINE | ID: mdl-35164357

ABSTRACT

Proteus mirabilis is a significant cause of urinary tract infection that may contribute to struvite stones. Anti-infection of this bacterium and anti-struvite formation must be considered. Sida acuta Burm. F. (SA) has been used for the treatment of diseases related to kidneys. Therefore, we investigated the effects of the SA leaf ethanolic extract (SAEE) on growth and on virulent factors (swarming motility and urease activity) of Proteusmirabilis isolated from kidney stone formers. We also evaluated anti-struvite crystal formation and phytochemical constituents of SAEE. The minimum inhibitory concentrations (MICs) of SAEE against three clinical P. mirabilis isolates were 8 mg/mL. Intriguingly, the 1/2MIC of SAEE had significant inhibitory effects on the swarming motility and urease activity of clinical P. mirabilis isolates when compared with the condition without SAEE. The SAEE at the various concentrations significantly inhibited the average weights of struvite crystals in a dose-dependent manner, compared with the control. The phytochemical analysis revealed that SAEE contained catechin, chlorogenic acid, rutin, and ferulic acid. This study indicated that SAEE has anti-P. mirabilis and anti-struvite crystal activities via its bioactive compounds. For this reason, SAEE may be developed as a new agent for the treatment of struvite stone induced by P. mirabilis.


Subject(s)
Phytochemicals/analysis , Phytochemicals/pharmacology , Plant Extracts/pharmacology , Proteus mirabilis/drug effects , Sida Plant/chemistry , Struvite/chemistry , Humans
17.
Cell Mol Biol (Noisy-le-grand) ; 67(3): 11-23, 2021 Nov 25.
Article in English | MEDLINE | ID: mdl-34933737

ABSTRACT

The use of plant extracts represents a promising approach for the synthesis of silver nanoparticles (AgNPs). This study reports the low-cost, green synthesis of AgNPs using the extract of clove and black seeds. The biosynthesized AgNPs were confirmed and characterized by analysis of the spectroscopy profile of the UV-visible spectrophotometer. The purpose of the present study is to evaluate the inhibitory effect concentration (MIC) of AgNPs, clove, and black cumin seed extracts on the growth and swarming of P. mirabilis. Clinical isolates of P. mirabilis were isolated from patients suffering from urinary tract infections. Thirteen types of antibiotics were used in the present study to detect their ability to inhibit P. mirabilis's resistance. Immunological findings included the determination of serum levels of IgG, IgM, IgA and complement protein C3 and C4. Results showed that IgG and IgA concentrations significantly increased (1311.13 ± 72.54 and 279 ± 21.31) respectively in UTI patients in comparison to the healthy control group which was 1089.88 ± 37.33 and 117.611 ± 4.19 respectively, While IgM concentrations were increased non significantly in UTI patients (153.331 ± 6.45) in comparison to healthy control (145.2 ± 13.49). Complement components C3 showed a significant increase in UTI patients with mean values of 125.95 ± 6.22 compared to the control group with mean values of 55.191 ± 9.64, while C4 showed statically non-significant among UTI patients in comparison with the control group (35.195 ± 2.34 and 34.371 ± 1.22) respectively.


Subject(s)
Complement System Proteins/metabolism , Immunoglobulins/blood , Metal Nanoparticles/administration & dosage , Plant Extracts/pharmacology , Proteus mirabilis/drug effects , Silver/administration & dosage , Urinary Tract Infections/blood , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antioxidants/administration & dosage , Antioxidants/pharmacology , Biofilms/drug effects , Biofilms/growth & development , Humans , Metal Nanoparticles/chemistry , Microbial Sensitivity Tests , Nigella sativa/chemistry , Plant Extracts/administration & dosage , Proteus mirabilis/genetics , Proteus mirabilis/physiology , Silver/chemistry , Spectrophotometry/methods , Spectroscopy, Fourier Transform Infrared/methods , Syzygium/chemistry , Urinary Tract Infections/metabolism , Urinary Tract Infections/microbiology
18.
J Nat Prod ; 84(12): 3011-3019, 2021 12 24.
Article in English | MEDLINE | ID: mdl-34842422

ABSTRACT

Six new nonadride derivatives, named talarodrides A-F (1-6), were isolated from the Antarctic sponge-derived fungus Talaromyces sp. HDN1820200. All structures including the absolute configurations were deduced by extensive spectroscopic analysis and computational ECD calculations. Compounds 1-4 share a rare caged bicyclo[4.3.1]-deca-1,6-diene with a bridgehead olefin and maleic anhydride core skeleton, while compounds 5 and 6 possess the first case of a naturally occurring 5/7/6 methanocyclonona[c]furan skeleton. Talarodride A (1) and talarodride B (2) showed selective inhibitory effects against Proteus mirabilis and Vibrio parahemolyticus with MICs of 3.13-12.5 µM.


Subject(s)
Anhydrides/isolation & purification , Porifera/microbiology , Talaromyces/chemistry , Anhydrides/chemistry , Anhydrides/pharmacology , Animals , Antarctic Regions , Microbial Sensitivity Tests , Proteus mirabilis/drug effects , Vibrio parahaemolyticus/drug effects
19.
Bol. latinoam. Caribe plantas med. aromát ; 20(6): 575-597, nov. 2021. ilus, tab
Article in English | LILACS | ID: biblio-1369745

ABSTRACT

This study investigated the antibacterial potential of Euphorbia hirtawhole plant extracts, honey and conventional antibiotics and their synergistic effects against selected multidrug resistant and typed bacterial strains associated with otitis media. E. hirtawhole plant extract was purified using column chromatography technique. The antibacterial assays of extracts were done using standard microbiological procedures. Protein, sodium and potassium ion leakage of the synergistic mixtures was determined using flame-photometry. At 100 mg/ml, acetone extracts presented highest inhibition against S. aureus (NCTC 6571) with 32 ± 0.83 mm zone of inhibition. The fractional inhibitory concentration indices displayed higher synergism in combination of plant extract, honey and ciprofloxacin against P. mirabilisat 0.02 compared to drug combination synergy standard (≤ 0.5). This work revealed augmentation of ciprofloxacin potency when combined with purified E. hirta acetone extract and honey and implies their high potential in the treatment of multidrug resistant infectionof otitis media.


Este estudio investigó el potencial antibacteriano de extractos de plantas enteras de Euphorbia hirta, miel y antibióticos convencionales y sus efectos sinérgicos contra cepas bacterianas seleccionadas multirresistentes y tipificadas asociadas con la otitis media. El extracto de la planta entera de E. hirtase purificó usando la técnica de cromatografía en columna. Los ensayos antibacterianos de extractos se realizaron utilizando procedimientos microbiológicos estándar. La fuga de iones de proteínas, sodio y potasio de las mezclas sinérgicas se determinó mediante fotometría de llama. A 100 mg/ml, los extractos de acetona presentaron la mayor inhibición contra S. aureus (NCTC 6571) con una zona de inhibición de 32 ± 0,83 mm. Los índices de concentración inhibitoria fraccional mostraron un mayor sinergismo en combinación de extracto de planta, miel y ciprofloxacina contra P. mirabilisa 0,02 en comparación con el estándar de sinergia de combinación de fármacos (≤ 0,5). Este trabajo reveló un aumento de la potencia de la ciprofloxacina cuando se combina con extracto de acetona purificado de E. hirtay miel e implica sualto potencial en el tratamiento de infecciones de otitis media resistentes a múltiples fármacos.


Subject(s)
Humans , Otitis Media/drug therapy , Plant Extracts/therapeutic use , Euphorbia/chemistry , Anti-Bacterial Agents/therapeutic use , Proteus mirabilis/drug effects , Staphylococcus aureus/drug effects , Terpenes/analysis , Flavonoids/analysis , Plant Extracts/pharmacology , Ciprofloxacin/pharmacology , Microbial Sensitivity Tests , Flame Emission Photometry , Chromatography, Thin Layer , Drug Resistance, Multiple , Drug Synergism , Glycosides/analysis , Honey , Gas Chromatography-Mass Spectrometry , Anti-Bacterial Agents/pharmacology
20.
Pak J Pharm Sci ; 34(3(Supplementary)): 1056-1062, 2021 May.
Article in English | MEDLINE | ID: mdl-34602432

ABSTRACT

Recent studies on prevalence of urinary tract infection indicate that approximately one third population of the world has been suffering from this disease. The current study was designed to evaluate the antibacterial activity of aqueous-ethanolic extracts (30/70) of Tribulus terrestris (TT), Vaccinium macrocarpon (VM), Cuminum cyminum (CC), Rheum emodi (RE), Piper cubeba (PC) and their compound formulation "Crano-cure" against Escherichia coli, Klebsiella pneumonia, Staphylococcus saprophyticus and Proteus mirabilis through disc diffusion method and agar well methods compared with standard Ciprofloxacin. DPPH radical scavenging methods were applied for antioxidant activities and phytochemical analysis was also performed to detect the phytoconstituents. All the plants exhibited potent antibacterial strength while Crano-cure showed most potent results comparable with that of standard drug. The zone of inhibition produced by disk diffusion test was 26±0.34, 26±0.75, 26±0.00, 18±0.64, 22.5±0.52, 29±0.39, 32±0.00 mm and for agar well diffusion test 23±0.67, 22±0.46, 23±0.77, 20±0.00, 22±0.46, 24±0.52, 33±0.00 mm against Tribulus terrestris, Cuminum cyminum, Rheum emodi, Piper cubeba, Vaccinium macrocarpon, crano-cure and ciprofloxacin. Similarly, percentage inhibition for antioxidant potential was 78.74, 24.57, 58.75, 20.23, 88.88, 90.12 and 92.35 respectively. The tested plants exhibited remarkable antibacterial and antioxidant activities.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antioxidants/pharmacology , Cuminum , Piper , Plant Extracts/pharmacology , Rheum , Tribulus , Vaccinium macrocarpon , Biphenyl Compounds , Ciprofloxacin/pharmacology , Disk Diffusion Antimicrobial Tests , Escherichia coli/drug effects , Indicators and Reagents , Klebsiella pneumoniae/drug effects , Picrates , Plant Extracts/chemistry , Plants, Medicinal , Proteus mirabilis/drug effects , Staphylococcus saprophyticus/drug effects , Urinary Tract Infections
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