Bacteriological and molecular study of fosfomycin resistance in uropathogenic Escherichia coli.

The identification of genes associated with resistance has the potential to facilitate the development of novel diagnostic tests and treatment methods. The objective of this study was to examine the antibiotic resistance and Fosfomycin resistance genes in uropathogenic Escherichia coli (UPEC) in patients in Baghdad, Iraq. After analyzing 250 urine samples using various identification methods, including the examination of morphological characteristics, biochemical tests, and genetic detection, it was determined that E. coli was the most common bacteria present, accounting for 63.6% of the samples. Antibiotic susceptibility testing showed a significant prevalence of resistance to various antibiotics, with 99.3% of E. coli isolates exhibiting multiple drug resistance (MDR). Fosfomycin showed antibacterial properties against UPEC. The minimum inhibitory concentration (MIC) ranged from 512 to 1024 µg/mL, while the minimum bactericidal concentration (MBC) was 2048 µg/mL. In the time-kill assay, fosfomycin was effective against fosfomycin-resistant isolates within 8-12 h. The genetic determinants associated with fosfomycin resistance were examined through the utilization of polymerase chain reaction (PCR). The findings indicated that the genes murA, glpT, and cyaA were detected in all the isolates when genomic DNA was used as a template. However, all the tests yielded negative results when plasmid was used as a template. The genes fosA3 and fosA4 were detected in 8.6% and 5% of the isolates when genomic DNA was used as a template. When plasmid was used as a template, the genes fosA3 and fosA4 were found in 5.7% and 2.9% of the isolates, respectively. In conclusion, there is an increasing problem with antibiotic resistance in UPEC, with elevated rates of resistance to several antibiotics. The study also offers novel insights into the genetic foundation of fosfomycin resistance in UPEC.

Antimicrobial resistance survey and whole-genome analysis of nosocomial P. Aeruginosa isolated from eastern Province of China in 2016-2021.

BACKGROUND: Pseudomonas aeruginosa is a major Gram-negative pathogen that can exacerbate lung infections in the patients with cystic fibrosis, which can ultimately lead to death. METHODS: From 2016 to 2021, 103 strains of P. aeruginosa were isolated from hospitals and 20 antibiotics were used for antimicrobial susceptibility determination. Using next-generation genome sequencing technology, these strains were sequenced and analyzed in terms of serotypes, ST types, and resistance genes for epidemiological investigation. RESULTS: The age distribution of patients ranged from 10 days to 94 years with a median age of 69 years old. The strains were mainly isolated from sputum (72 strains, 69.9%) and blood (14 strains, 13.6%). The size of these genomes ranged from 6.2 Mb to 7.4 Mb, with a mean value of 6.5 Mb. In addition to eight antibiotics that show inherent resistance to P. aeruginosa, the sensitivity rates for colistin, amikacin, gentamicin, ceftazidime, piperacillin, piperacillin-tazobactam, ciprofloxacin, meropenem, aztreonam, imipenem, cefepime and levofloxacin were 100%, 95.15%, 86.41%, 72.82%, 71.84%, 69.90%, 55.34%, 52.43%, 50.49%, 50.49%, 49.51% and 47.57% respectively, and the carriage rate of MDR strains was 30.69% (31/101). Whole-genome analysis showed that a total of 50 ST types were identified, with ST244 (5/103) and ST1076 (4/103) having a more pronounced distribution advantage. Serotype predictions showed that O6 accounted for 29.13% (30/103), O11 for 23.30% (24/103), O2 for 18.45% (19/103), and O1 for 11.65% (12/103) of the highest proportions. Notably, we found a significantly higher proportion of ExoU in P. aeruginosa strains of serotype O11 than in other cytotoxic exoenzyme positive strains. In addition to this, a total of 47 crpP genes that mediate resistance to fluoroquinolones antibiotics were found distributed on 43 P. aeruginosa strains, and 10 new variants of CrpP were identified, named 1.33, 1.34, 1.35, 1.36, 1.37, 1.38, 1.39, 1.40, 1.41 and 7.1. CONCLUSIONS: We investigated the antibiotic susceptibility of clinical isolates of P. aeruginosa and genomically enriched the diversity of P. aeruginosa for its prophylactic and therapeutic value.

Integron distribution and relationship to antimicrobial resistance in E. coli isolated from blood culture.

PURPOSE: The aim of this study was to evaluate the distribution of integrons in strains of E. coli isolated from blood culture and the relationship between integrons and antimicrobial resistance. METHODS: The study included 100 E. coli strains sent to the Medical Microbiology Laboratory from different clinics between September 2022 and June 2023. Antibiotic susceptibility was evaluated according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST). The presence of integrons was determined by the inhouse polymerase chain reaction (PCR). RESULTS: Integron positivity was detected in 45 (45%) of isolates, and class 1 integrons were found in 41 (41%), class 2 integrons in 2 (2%), and both class 1 integrons and class 2 integrons in 2 (2%). Class 3 integron positivity was not detected. In total, 63 cases of community origin and 37 cases of hospital origin were identified. When antibiotic resistance was evaluated, the highest sensitivity was noted for amikacin (1%), meropenem (5%), imipenem (6%), and the highest resistant antibiotics were ampicillin (82%), cepfuroxime sodium (65%), and amoxicillin/clavulanate (62%), respectively. Of the 16 antimicrobial substances evaluated, 10 had an antibiotic resistance rate of over 45%. In class 1 integron-positive samples, ampicillin resistance and trimethoprim/sulfamethoxazole resistance were higher than in negative samples (p = 0.02, p = 0.0001, respectively). Fifty-one (51%) samples were found to have multiple drug resistance (MDR). In total, 59.5% of hospital-acquired isolates and 46% of community-acquired isolates were considered to be MDR. The class 1 integron positivity in MDR samples was high (p = 0.038). CONCLUSION: The high MDR rates in both hospital-acquired and community-acquired isolates are alarming. In particular, class 1 integron monitoring is very important to prevent the spread of MDR isolates.

Computational Study of Antimicrobial Peptides for Promising Therapeutic Applications Against Methicillin-resistant Staphylococcus Aureus.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a causative agent for multiple drug-resistant diseases and is a prime health concern. Currently, antibiotics like vancomycin, daptomycin, fluoroquinolones, linezolid, fifth-generation cephalosporin and others are available in the market for the treatment of MRSA infection. METHODS: With the increasing prevalence of drug-resistant cases, researchers are actively investigating alternative strategies to combat MRSA, including the exploration of peptide therapeutics. This study employed computational methods to prospect for potential Antimicrobial Peptides (AMPs). RESULTS: A total of One hundred and fifty antimicrobial peptides were explored based on physicochemical properties. The results showed that Clavanin B was the most appropriate candidate. Molecular Docking and Molecular Dynamics Simulation results showed the protein-peptide interaction of the MRSA target proteins, Penicillin Binding Protein 2a and Panton-Valentine Leukocidin Toxin, with the Antimicrobial Peptide Clavanin B. CONCLUSION: Currently, the antimicrobial peptide database highlights Clavanin B's role as an anti-HIV peptide. Moreover, this investigation proposes Clavanin B as a viable repurposed drug for treating MRSA, underscoring its potential deployment in the management of MRSA infections.

An Overview of the Global Alarming Increase of Multiple Drug Resistant: A Major Challenge in Clinical Diagnosis.

The increased spreading of antibiotic resistance among different infectious agents has been a fast-growing public health challenge worldwide; this is because of the discovery of new resistance mechanisms and the reduction in quality and effective treatments of general pathogenic infections. This has caused unsuccessful microbial responses to standard therapy, which could lead to a higher risk of mortality, prolonged illness, and more expenditures for health care. Most parasites, bacteria, fungi, and viruses can produce a higher degree of multidrug resistance (MDR) with increased mortality and morbidity. Moreover, the establishment of MDR can be a natural phenomenon, improper utilization of antimicrobial drugs, lack of proper sanitary conditions, poor method of food handling, and absence of infection prevention and control (IPC), which could be responsible for the further spreading of MDR. Moreover, MDR helminth's mechanism of action can occur via genetic alterations in the drug transport, metabolisms and target sites. MDR bacterial mode of action such as cell wall synthesis inhibitors, DNA synthesis inhibitors and so on. However, there have been different approaches to managing and preventing multi-drug resistance. Hence, this review's aim is to educate the public about the global increase of multiple drug resistance and the danger ahead if appropriate measures are not put in place to combat microbial infections.

Acori Tatarinowii Rhizoma prevents the fluoxetine-induced multiple-drug resistance of Escherichia coli against antibiotics.

BACKGROUND: In treating depression, the residual anti-depressant in gut interacts with the microbiome, leading to the appearance of multiple drug resistant (MDR) mutants, which poses a challenge for the treatment of infectious complications. Strategy is needed to combat this issue. Acori Tatarinowii Rhizoma (ATR, rhizome of Acorus tatarinowii Schott, Araceae), a traditional Chinese medicine, has been widely used for treatment of neurological disorders and gastrointestinal digestive disease in China. Here, ATR was demonstrated an excellent MDR-preventing effect in fluoxetine-induced Escherichia coli (E. coli). AIM OF THE STUDY: This study aimed to reveal the effective role of ATR and its signaling cascades involved in preventing fluoxetine-induced MDR. MATERIALS AND METHODS: The water extract of ATR was co-applied with sub-minimum inhibitory concentration (100 mg/l) of fluoxetine in E. coli to evaluate its anti-MDR potential. Formation of reactive oxygen species (ROS) and expression of MDR-related genes in bacteria were measured by dichloro-dihydro-fluorescein diacetate assay and real-time PCR, respectively. Two fluorescent dyes, 1-N-phenylnapthylamine and 3,3'-dipropylthiadicarbocyanine were used to analyze the outer membrane permeability and inner membrane depolarization of E. coli. The accumulation of fluoxetine in the treated E. coli was determined via HPLC. The active fraction of ATR was identified. RESULTS: The water extract of ATR significantly decreased the number of MDR mutants induced by fluoxetine and had half effective concentrations (EC50) of 55.5 µg/ml and 16.8 µg/ml for chloramphenicol and tetracycline, respectively. ATR robustly reversed the fluoxetine-induced superoxide response and membrane damage in E. coli. In addition, the inclusion of ATR significantly reduced the accumulation of fluoxetine in E. coli. After further fractionation, the polysaccharide of ATR was demonstrated as the fraction with the most significant anti-MDR activity. CONCLUSIONS: This is the first report to investigate the MDR-preventing effect of ATR. The results of this study proposed ATR as an excellent herbal product to prevent MDR issues, as induced by fluoxetine, with the potential to reduce the side effects during the drug therapy of depression.

Screening for multidrug-resistant organisms in high-risk hospitalized patients with hematologic diseases.

OBJECTIVES: Patients treated for hematologic malignancies are at higher risk for blood stream infections (BSI) and multidrug-resistant organisms (MDRO) are increasingly involved. Studies showed a significant association between rectal colonization status and a higher risk of subsequent MDRO BSI. The objective of our study was to probe the practice of surveillance cultures in Belgian hematology centers. METHODS: A questionnaire was sent to the 13 hematology centers participating in the acute leukemia board of the Belgian Hematology Society. 21 questions probed for the method of surveillance cultures, MDRO screened, antimicrobial prophylaxis, and empirical therapy and their relationship with colonization status. RESULTS: All centers completed the questionnaire in full. Routine gastrointestinal surveillance cultures in hematologic patients are taken in 10 hospitals. Organisms tested for included mostly ESBL (n = 9) and carbapenem-resistant (n = 8) Enterobacterales. All centers with a screening strategy adapt empiric antibiotic therapy based on MDRO colonization. Prophylaxis strategies are variable, only two centers adapt prophylaxis upon documentation of fluoroquinolone resistance. CONCLUSIONS: The majority of the Belgian centers perform routine surveillance cultures and adapt empiric therapy for neutropenic fever accordingly. Other reasons for testing include to gain insight into local epidemiology and to prevent in-hospital transmission. In general, there was significant variability in surveillance dimensions.

Prevalence and antimicrobial resistance profile of pathogens isolated from patients with urine tract infections admitted to a university hospital in a medium-sized Brazilian city

ABSTRACT This study aimed to determine the antibiotic profile of microorganisms isolated from urine samples of patients with community urine tract infections (UTI) admitted to the University Hospital of the Federal University of Sao Carlos to support an appropriate local empirical treatment. A retrospective cross-sectional study was conducted from October 2018 to October 2020. Data from 1,528 positive urine cultures for bacterial pathogens and antibiograms were tabulated. Bacterial species prevalence and their resistance profile were analyzed and compared by sex and age. For Gram-negative fermenting bacteria, resistance rates were compared between patients with previous hospitalization and the total of infections caused by this group. For comparisons, the Chi-square test was performed, using Fisher's exact test when necessary (BioEstat program, adopting p ≤ 0.05). A multivariate analysis was applied to assess the effect of the studied variables in predicting multidrug resistance. Infections were more prevalent in women and older adults. Gram-negative bacteria represented 90.44% of total cultures. In both sexes, E. coli prevalence was significantly higher in adults compared with older adults (p < 0.0001). For several antibiotics, resistance rates were higher in the older adults compared with other ages and in patients with Gram-negative fermenting infections and previous hospitalization compared with the total of infections by this group of bacteria. The closer to the hospitalization, the higher the number of antibiotics with superior resistance rates. Resistance rates for aminoglycosides, carbapenems, ceftazidime, nitrofurantoin, piperacillin+tazobactam, and fosfomycin were less than 20%, considered adequate for empirical treatment. Only hospitalization in the previous 90 days was statistically significant in predicting infections by multidrug-resistant bacteria.

The secrets of environmental Pseudomonas aeruginosa in slaughterhouses: Antibiogram profile, virulence, and antibiotic resistance genes.

Environmental pollution is a serious problem that can cause sicknesses, fatality, and biological contaminants such as bacteria, which can trigger allergic reactions and infectious illnesses. There is also evidence that environmental pollutants can have an impact on the gut microbiome and contribute to the development of various mental health and metabolic disorders. This study aimed to study the antibiotic resistance and virulence potential of environmental Pseudomonas aeruginosa (P. aeruginosa) isolates in slaughterhouses. A total of 100 samples were collected from different slaughterhouse tools. The samples were identified by cultural and biochemical tests and confirmed by the VITEK 2 system. P. aeruginosa isolates were further confirmed by CHROMagar™ Pseudomonas and genetically by rpsL gene analysis. Molecular screening of virulence genes (fimH, papC, lasB, rhlI, lasI, csgA, toxA, and hly) and antibiotic resistance genes (blaCTX-M, blaAmpC, blaSHV, blaNDM, IMP-1, aac(6')-Ib-, ant(4')IIb, mexY, TEM, tetA, and qnrB) by PCR and testing the antibiotic sensitivity, biofilm formation, and production of pigments, and hemolysin were carried out in all isolated strains. A total of 62 isolates were identified as P. aeruginosa. All P. aeruginosa isolates were multidrug-resistant and most of them have multiple resistant genes. blaCTX-M gene was detected in all strains; 23 (37.1%) strains have the ability for biofilm formation, 33 strains had virulence genes, and 26 isolates from them have more than one virulence genes. There should be probably 60 (96.8%) P. aeruginosa strains that produce pyocyanin pigment. Slaughterhouse tools are sources for multidrug-resistant and virulent pathogenic microorganisms which are a serious health problem. Low-hygienic slaughterhouses could be a reservoir for resistance and virulence genes which could then be transferred to other pathogens.

Beta-lactam, aminoglycoside, and quinolone resistance in Escherichia coli strains isolated from shrimps and mussels in the Marmara Sea.

The purpose of the study was to examine the prevalence of Escherichia coli in shrimps and mussels, and to determine the distribution of ß-lactam, aminoglycoside, quinolone, and multi-drug resistance phenotypically and genotypically in E. coli isolates obtained from mussels and shrimps in Istanbul. Faecal samples were collected from mussels (n = 96) and shrimps (n = 96) from the Marmara Sea coastline and fish markets in Istanbul. For the detection of antibiotic susceptibilities, seven antibiotic groups were used. ß-lactamase, aminoglycoside, and quinolone genes were also determined. A total of 34 (17.7%, 15 shrimps, and 19 mussels) E. coli were isolated, and 17 (50%) were found to be resistant to one or more antimicrobials. The highest resistance was seen against aminoglycosides with 11 isolates (32.35%), followed by quinolones with 10 isolates (29.41%) and extended-spectrum ß-lactamase (ESBL) with 4 isolates (11.76%). Multi-drug resistance was detected in 5 isolates (14.7%) from 3 shrimp and 2 mussel samples. The prevalence of ESBL genes was demonstrated at 3.84% in mussels and shrimp samples. There were no AmpC and carbapenemase-producing genes. These samples harbored blaCTX-M-1 (n = 3) and blaTEM (n = 4). Ten isolates were resistant to aminoglycosides genotypically. Resistance genes detected were strB in 2 isolates, aadA in 5, strB and aadA together in 3, ANT('')-Ia, aphA1 and aphA2 simultaneously in 3, aphA1 in 1, aac(3)-IIa in 1 isolate. aac(6')-Ib-cr gene was detected in only one of 10 phenotypically resistant isolates to quinolones.

Dynamics of antimicrobial resistance and virulence of staphylococcal species isolated from foods traded in the Cape Coast metropolitan and Elmina municipality of Ghana.

The impact of staphylococci on food poisoning and infections could be higher than previously reported. In this study, we characterised the occurrence and coexistence of antimicrobial resistance and virulence genes of staphylococci isolates in foods. Staphylococci were isolated from 236 samples of selected street-vended foods and identified. The pattern of antimicrobial resistance and virulence genes in the staphylococci were assessed using disc diffusion, PCR and analysis of next-generation sequencing data. The food samples (70.76 %) showed a high prevalence of staphylococci and differed among the food categories. Forty-five Staphylococcus species were identified and comprised coagulase-negative and positive species. Staphylococcus sciuri (now Mammaliicoccus sciuri), S. aureus, S. kloosii, S. xylosus, S. saprophyticus, S. haemolyticus and S. succinus were the most abundant species. The staphylococcal isolates exhibited resistance to tetracycline, levofloxacin, ciprofloxacin, norfloxacin, gentamicin and amikacin and susceptibility to nitrofurantoin. Antimicrobial susceptibilities were also reported for cefoperazone, ceftriaxone, cefotaxime, nalidixic acid and piperacillin-tazobactam. The antimicrobial resistance and virulence genes commonly detected consisted of tet, arl, macB, van, gyr, nor, optrA, bcrA, blaZ, taeA and S. aureus lmrS. The isolates frequently exhibited multiple resistance (30.42 %) of up to eight antimicrobial drug classes. The isolates predominantly harboured genes that express efflux pump proteins (50.53 %) for antibiotic resistance compared with inactivation (10.05 %), target alteration (26.72 %), protection (7.67 %) and replacement (3.17 %). The virulence determinants comprised genes of pyrogenic toxin superantigens (eta, etb, tst), adhesions (clf, fnbA, fnbB, cna, map, ebp, spA, vWbp, coa) and genes that express exoproteins (nuclease, metalloprotease, γ-hemolysin, hyaluronate lyase). There was a statistically significant difference in the prevalence of staphylococci isolates and their antimicrobial resistance and virulence profile as revealed by the phenotypic, PCR and next-generation sequencing techniques. The findings suggest a higher health risk for consumers. We recommend a critical need for awareness and antimicrobial susceptibility and anti-virulence strategies to ensure food safety and counteract the spread of this clinically relevant genus.

Cell-to-cell transmission promotes the emergence of double-drug resistance.

The use of multiple antivirals in a single patient increases the risk of emergence of multidrug-resistant viruses, posing a public health challenge and limiting management options. Cell-to-cell viral transmission allows a pair of viruses that are each resistant to a single drug to persist for a prolonged period of passages although neither can survive alone under double-drug treatment. This pair should then persist until they accumulate a second mutation to generate resistance to both drugs. Accordingly, we here propose a hypothesis that viruses have a much higher probability of developing double-drug resistance when they are transmitted via a cell-to-cell mode than when they are transmitted via a cell-free mode through released virions. By using a stochastic model describing the changes in the frequencies of viral genotypes over successive infections, we analytically demonstrate that the emergence probability of double resistance is approximately the square of the number of viral genomes that establish infection times greater in cell-to-cell transmission than in cell-free transmission. Our study suggests the importance of inhibiting cell-to-cell transmission during multidrug treatment.

Antibacterial mechanism of action and in silico molecular docking studies of Cupressus funebris essential oil against drug resistant bacterial strains.

The primary objective of this research work was to study the antibacterial effects of Cupressus funebris essential oil (EO) against various drug resistant bacterial pathogens along with studying the molecular docking interactions of the major components of the EO with the key bacterial proteins/enzymes. Gas chromatography-mass spectrometry was used to analyse the chemical composition of the Cupressus funebris EO. The initial antibacterial screening was performed by using disc diffusion and microdilution methods. Scanning electron microscopy was also performed in order to study effects of the EO on bacterial cell morphology. Further, molecular docking studies were performed using Autodock Vina and results were visualised by BIOVIA Discovery Studio. The chemical composition of the EO showed the presence of 15 components with citronellal, terpinene-4-ol, α-phellandrene and 1,8-cineole as the major components of the EO. Results indicated that the EO of Cupressus funebris exhibited dose-dependent as well as time dependent antibacterial effects. The scanning electron microscopy indicated that the Cupressus funebris EO led to membrane rupture and permeabilization of the bacterial cells. Molecular docking studies indicated that the major compounds of the EO (citronellal and terpinene-4ol) showed strong interactions with the active site of the bacterial DNA gyrase enzyme explaining the antibacterial mode of action of the EO. Ciprofloxacin was also used for docking which showed stronger interactions with the target protein than citronellal or terpinene-4-ol. In conclusion, the major findings of the current study were that the EO of Cupressus funebris causes bacterial membrane rupture and permeabilization, shows time-dependent and dose-dependent antibacterial action, along with interacting with crucial bacterial enzyme viz., DNA gyrase as indicated by molecular docking studies.

High burden of MDR, XDR, PDR, and MBL producing Gram negative bacteria causing infections in Kermanshah health centers during 2019-2020.

Background and Objectives: Microorganisms producing Metallo-Beta-Lactamase (MBL) are a threat and cause of concern as they have become one of the most feared resistance mechanisms. This study was designed to explore the prevalence of MBL production in clinical isolates of Gram negative bacteria using phenotypic MBL detection. Materials and Methods: A total of 248 isolates were collected from various clinical samples and were evaluated for carbapenem resistance and MBL production. All strains were screened for MBL production using Double Disk Confirmatory Test (DDCT). Results: The results of screening for MBL production using phenotypic disk diffusion method showed that in the 85 isolates were carbapenemase positive; including, 10 (16.1%) Klebsiella pneumoniae, 9 (14.5%) Escherichia coli, 58 (93.6%) Acinetobacter baumannii, and 8 (12.9%) Pseudomonas aeruginosa isolates. Also, 83 (97.6) Carbapenemase-producing isolates were resistant to at least four classes of antimicrobials (MDR). Conclusion: A. baumannii was the most common carbapenem resistant bacterium in medical centers in Kermanshah. Significant multiple drug resistance (MDR) incidence was observed compared to different classes of antibiotics.

Scorpionfish BPI is highly active against multiple drug-resistant Pseudomonas aeruginosa isolates from people with cystic fibrosis.

Chronic pulmonary infection is a hallmark of cystic fibrosis (CF) and requires continuous antibiotic treatment. In this context, Pseudomonas aeruginosa (Pa) is of special concern since colonizing strains frequently acquire multiple drug resistance (MDR). Bactericidal/permeability-increasing protein (BPI) is a neutrophil-derived, endogenous protein with high bactericidal potency against Gram-negative bacteria. However, a significant range of people with CF (PwCF) produce anti-neutrophil cytoplasmic antibodies against BPI (BPI-ANCA), thereby neutralizing its bactericidal function. In accordance with literature, we describe that 51.0% of a total of 39 PwCF expressed BPI-ANCA. Importantly, an orthologous protein to human BPI (huBPI) derived from the scorpionfish Sebastes schlegelii (scoBPI) completely escaped recognition by these autoantibodies. Moreover, scoBPI exhibited high anti-inflammatory potency towards Pa LPS and was bactericidal against MDR Pa derived from PwCF at nanomolar concentrations. In conclusion, our results highlight the potential of highly active orthologous proteins of huBPI in treatment of MDR Pa infections, especially in the presence of BPI-ANCA.

Cystic fibrosis is a genetic disorder that makes people produce unusually thick and sticky mucus that clogs their lungs and airways. This inevitably leads to recurring bacterial infections, particularly those caused by the Gram-negative bacterium Pseudomonas aeruginosa. Antibiotics are needed to treat these infections. However, over time most bacteria build modes of resistance to these drugs and, once multiple drug-resistant bacteria colonize the lung, very limited treatment options are left. Therefore, new therapeutic approaches are desperately needed. Notably, humans themselves express a highly potent antimicrobial protein called BPI (short for Bactericidal/permeability­increasing protein) that attacks Gram-negative bacteria, including multiple drug-resistant strains of P. aeruginosa. Unfortunately, many people with cystic fibrosis also generate antibodies that bind to BPI and interfere with its antimicrobial function. Faced with this conundrum, Holzinger et al. set out to find BPIs made by other animals which might not be recognized by human antibodies and also display a high potential to attack Gram-negative bacteria. Based on specific selection criteria, Holzinger et al. focused their attention on BPI made by scorpionfish, a type of venomous fish that live near coral reefs. Compared to other BPI proteins they investigated, the one produced by scorpionfish appeared to be the most capable of binding to P. aeruginosa via a prominent surface molecule exclusively found on Gram-negative bacteria. Furthermore, when Holzinger et al. tested whether the antibodies present in people with cystic fibrosis could recognize scorpionfish BPI, they found that the BPI completely evaded detection. The scorpionfish BPI was also able to pre-eminently attack P. aeruginosa. In fact, it was even able to potently kill drug-resistant strains of the bacteria that had been isolated from people with cystic fibrosis. This study suggests that scorpionfish BPI could serve as an alternative to antibiotics in people with cystic fibrosis that have otherwise untreatable bacterial infections. Drug-resistant bacteria which cause life threatening conditions are on the rise across the globe, and scorpionfish BPI could be a potential candidate to treat affected patients. In the future, animal experiments will be needed to explore how highly potent non-human BPIs function in whole living organisms.

Evaluation of donor-derived bacterial infections in lung transplant recipients.

Background: This study aims to evaluate the etiology and outcomes of donor-derived bacterial infections in patients undergoing lung transplantation. Methods: Between January 2013 and December 2017, a total of 71 lung transplant recipients (56 males, 15 females; median age: 43.3 years) were retrospectively analyzed. The diagnosis of donor-derived bacterial infection was defined as the isolation of the same bacteria with the same antibiotic susceptibility patterns in a lung sample of donor and in one sample obtained from patients after transplantation and the presence of clinical evidence of infection. Results: Ten (14%) patients were found to have donor-derived bacterial infection. Acinetobacter baumannii was found in three, Pseudomonas aeruginosa in three, Klebsiella pneumoniae in one, Enterobacter cloacae in one, Staphylococcus aureus in one, and both Klebsiella pneumoniae and Acinetobacter baumannii in one patient. Twenty-four of lung-transplant recipients and four patients with donor-derived infection died. Conclusion: Lung transplants are usually performed in hospitalized patients or in those admitted to the intensive care unit. These patients commonly experience infection and colonization with resistant microorganisms.

A case series and literature review of infections due to Myroides spp.: identification of contributing factors and emerging antibiotic susceptibility trends.

Introduction: Infections forby Myroides spp. can lead to significant morbidity and mortality, particularly in immunocompromised patients with underlying co-morbidities. Recent reports have highlighted its intrinsic and acquired drug resistance, making it a particularly challenging infectious agent to combat. Methods: Myroides spp. isolated and reported in clinically significant urine samples were considered for the study. Identification of the organism was done via the VITEK 2C system. Antibiotic susceptibility testing was done using both manual and automated methods following Clinical and Laboratory Standards Institute (CLSI) guidelines. Existing literature was searched on MEDLINE using PubMed. Results: We present a series of five catheter-associated urinary tract infections due to Myroides odoratimimus , with sensitivity to only minocycline. This is the first case from Western India, and the third case in the existing literature that shows Myroides sensitivity only to minocycline. Our literature review is the first to systematically describe contributory factors to infection, allowing us to devise a clinically relevant tool that delineates contributory factors and efficacious drugs in Myroides spp. infection. Conclusion: Myroides spp. infections, previously considered rare and opportunistic, need cognizance and diagnostic suspicion especially in particular associated conditions.

[Urinary tract infections including pyelonephritis]. / Harnwegsinfektionen einschließlich Pyelonephritis.

Urinary tract infections (UTIs) are among the most common bacterial infections. The clinical phenotypes of UTIs are heterogeneous, ranging from rather benign uncomplicated infections to complicated UTIs and pyelonephritis to severe urosepsis. There has been a sharp increase in the incidence of severe UTIs, whilst the incidence of sepsis in general is declining. The classifications of UTIs partially differ between clinical and regulatory claims. Experience has also been gained over the last few years to define the appropriate endpoints that are used in clinical studies. Above all, patient-centered evaluation strategies of the endpoints were developed, in order to be able to identify the advantages of new antibiotics compared to traditional antibiotics. The development of new antibiotics for UTIs is essential, since multidrug-resistant enterobacteria, which belong to the typical bacterial spectrum of UTIs, are frequently associated with mortality from infections. In recent years, several new antibiotics/combinations that are particularly effective against multi-resistant gram-negative pathogens have been investigated for the treatment of UTIs.

It is the time for quorum sensing inhibition as alternative strategy of antimicrobial therapy.

Multiple drug resistance poses a significant threat to public health worldwide, with a substantial increase in morbidity and mortality rates. Consequently, searching for novel strategies to control microbial pathogenicity is necessary. With the aid of auto-inducers (AIs), quorum sensing (QS) regulates bacterial virulence factors through cell-to-cell signaling networks. AIs are small signaling molecules produced during the stationary phase. When bacterial cultures reach a certain level of growth, these molecules regulate the expression of the bound genes by acting as mirrors that reflect the inoculum density.Gram-positive bacteria use the peptide derivatives of these signaling molecules, whereas Gram-negative bacteria use the fatty acid derivatives, and the majority of bacteria can use both types to modulate the expression of the target gene. Numerous natural and synthetic QS inhibitors (QSIs) have been developed to reduce microbial pathogenesis. Applications of QSI are vital to human health, as well as fisheries and aquaculture, agriculture, and water treatment. Video Abstract.

Tyrosol induces multiple drug resistance in yeast Saccharomyces cerevisiae.

In yeast, multiple (pleiotropic) drug resistance (MDR) transporters efflux xenobiotics from the cytoplasm to the environment. Additionally, upon the accumulation of xenobiotics in the cells, MDR genes are induced. At the same time, fungal cells can produce secondary metabolites with physico-chemical properties similar to MDR transporter substrates. Nitrogen limitation in yeast Saccharomyces cerevisiae leads to the accumulation of phenylethanol, tryptophol, and tyrosol, which are products of aromatic amino acid catabolism. In this study, we investigated whether these compounds could induce or inhibit MDR in yeast. Double deletion of PDR1 and PDR3 genes, which are transcription factors that upregulate the expression of PDR genes, reduced yeast resistance to high concentrations of tyrosol (4-6 g/L) but not to the other two tested aromatic alcohols. PDR5 gene, but not other tested MDR transporter genes (SNQ2, YOR1, PDR10, PDR15) contributed to yeast resistance to tyrosol. Tyrosol inhibited the efflux of rhodamine 6G (R6G), a substrate for MDR transporters. However, preincubating yeast cells with tyrosol induced MDR, as evidenced by increased Pdr5-GFP levels and reduced yeast ability to accumulate Nile red, another fluorescent MDR-transporter substrate. Moreover, tyrosol inhibited the cytostatic effect of clotrimazole, the azole antifungal. Our results demonstrate that a natural secondary metabolite can modulate yeast MDR. We speculate that intermediates of aromatic amino acid metabolites coordinate cell metabolism and defense mechanisms against xenobiotics.