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1.
Int J Biol Macromol ; 279(Pt 3): 135253, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39244118

ABSTRACT

The rise of antimicrobial resistance has positioned ESKAPE pathogens as a serious global health threat, primarily due to the limitations and frequent failures of current treatment options. This growing risk has spurred the scientific community to seek innovative antibiotic therapies and improved oversight strategies. This review aims to provide a comprehensive overview of the origins and resistance mechanisms of ESKAPE pathogens, while also exploring next-generation treatment strategies for these infections. In addition, it will address both traditional and novel approaches to combating antibiotic resistance, offering insights into potential new therapeutic avenues. Emerging research underscores the urgency of developing new antimicrobial agents and strategies to overcome resistance, highlighting the need for novel drug classes and combination therapies. Advances in genomic technologies and a deeper understanding of microbial pathogenesis are crucial in identifying effective treatments. Integrating precision medicine and personalized approaches could enhance therapeutic efficacy. The review also emphasizes the importance of global collaboration in surveillance and stewardship, as well as policy reforms, enhanced diagnostic tools, and public awareness initiatives, to address resistance on a worldwide scale.


Subject(s)
Anti-Bacterial Agents , Humans , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial/drug effects , Bacteria/drug effects , Bacterial Infections/drug therapy , Bacterial Infections/microbiology
2.
Arch Microbiol ; 206(10): 397, 2024 Sep 09.
Article in English | MEDLINE | ID: mdl-39249569

ABSTRACT

Amongst all Enterococcus spp., E. faecalis and E. faecium are most known notorious pathogen and their biofilm formation has been associated with endocarditis, oral, urinary tract, and wound infections. Biofilm formation involves a pattern of initial adhesion, microcolony formation, and mature biofilms. The initial adhesion and microcolony formation involve numerous surface adhesins e.g. pili Ebp and polysaccharide Epa. The mature biofilms are maintained by eDNA, It's worth noting that phage-mediated dispersal plays a prominent role. Further, the involvement of peptide pheromones in regulating biofilm maintenance sets it apart from other pathogens and facilitating the horizontal transfer of resistance genes. The role of fsr based regulation by regulating gelE expression is also discussed. Thus, we provide a concise overview of the significant determinants at each stage of Enterococcus spp. biofilm formation. These elements could serve as promising targets for antibiofilm strategies.


Subject(s)
Biofilms , Enterococcus , Gram-Positive Bacterial Infections , Enterococcus/genetics , Enterococcus/metabolism , Gene Expression Regulation, Bacterial , Gram-Positive Bacterial Infections/epidemiology , Gram-Positive Bacterial Infections/microbiology , Gram-Positive Bacterial Infections/physiopathology , Bacterial Adhesion/genetics , Adhesins, Bacterial/genetics , Adhesins, Bacterial/metabolism , Polysaccharides, Bacterial/metabolism , Gene Transfer, Horizontal
3.
Antibiotics (Basel) ; 13(9)2024 Sep 21.
Article in English | MEDLINE | ID: mdl-39335074

ABSTRACT

BACKGROUND/OBJECTIVES: ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) pose a serious public health threat as they are resistant to multiple antimicrobial agents. Bloodstream infections (BSIs) caused by ESKAPE bacteria have high mortality rates due to the limited availability of effective antimicrobials. This study aimed to evaluate the prevalence and susceptibility of ESKAPE pathogens causing BSIs over three years in a large tertiary hospital in Salerno. METHODS: Conducted at the Clinical Microbiology Laboratory of San Giovanni di Dio e ''Ruggi D'Aragona'' Hospital from January 2020 to December 2022, blood culture samples from different departments were incubated in the BD BACTEC™ system for 5 days. Species identification was performed using MALDI-TOF MS, and antimicrobial resistance patterns were determined by the VITEK2 system. RESULTS: Out of 3197 species isolated from positive blood cultures, 38.7% were ESKAPE bacteria. Of these, 59.9% were found in blood culture samples taken from men, and the most affected age group was those aged >60 years. (70.6%). Staphylococcus aureus was the main BSI pathogen (26.3%), followed by Klebsiella pneumoniae (15.8%). Significant resistance rates were found, including 35% of Staphylococcus aureus being resistant to oxacillin and over 90% of Acinetobacter baumannii being resistant to carbapenems. CONCLUSIONS: These results highlight the urgent need for antimicrobial stewardship programs to prevent incurable infections.

4.
Pathogens ; 13(9)2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39338978

ABSTRACT

The leading cause of hospital-acquired infections worldwide includes Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. (ESKAPE) infections. These bacteria are commonly isolated from clinical settings and linked to a number of potentially fatal diseases associated with hospitals. The objective of this study was to review the prevalence of ESKAPE pathogens in Africa. We gathered and systematically reviewed the literature concerning the prevalence of ESKAPE pathogens, published in the English language from January 2014 to February 2024, from three databases (PubMed, Web of Science and ScienceDirect). Our overall results revealed that S. aureus was the most prevalent species (79.5%), followed by A. baumannii (27.6%), K. pneumoniae (24.2%), Enterobacter spp. (20%), P. aeruginosa (9.0%), and E. faecium (5.1%). Moreover, stool samples had the highest Pooled Prevalence Estimates (PPEs) of 44.0%, followed by urine, nasal, and blood samples with 37.3%, 26.9%, and 22.9%, respectively. For the diagnostic method used to identify these ESKAPE pathogens, VITEK-MS had the highest PPE of 55.2%, followed by whole genome sequencing and PCR with 37.1% and 33.2%, respectively. The highest PPE of ESKAPE pathogens was recorded in West Africa with 77.3%, followed by Central/Middle Africa and East Africa with 43.5% and 25.1%, respectively. The overall PPE of ESKAPE pathogens from humans, animals, the environment (water, soil, and surfaces) and food sources was 35.8%, 37.3%, 47.7%, and 34.2%, respectively. Despite their prevalence in nosocomial settings, studies have shown that the ESKAPE pathogens may be isolated from a range of environmental reservoirs, including soil, dumping sites, beach sand, wastewater, food, and fish farms, among others. This wide source of ESKAPE pathogens substrates indicates the need for a multidisciplinary collaborative partnership for epidemiological studies and intervention efforts by the human, veterinary, and environmental health sectors in Africa.

5.
Discov Nano ; 19(1): 154, 2024 Sep 23.
Article in English | MEDLINE | ID: mdl-39313578

ABSTRACT

Acinetobacter baumannii, an opportunistic pathogen has shown an upsurge in its multi-drug resistant isolates. OmpA of A. baumannii induces incomplete autophagy and apoptosis in host cells. Various therapeutic alternatives are under investigation against A. baumannii. Here, the major emphasis has been laid on comparing the efficacy of AgNP with different capping agents. OmpA targeted lead, Ivermectin capped AgNP (IVM-AgNP) has been compared with the antibacterial polyvinylpyrrolidone capped AgNP (PVP-AgNP) for their role in the modulations of host autophagy. Upregulation of p62 and LC3B confirmed by real-time PCR analysis indicated an increased autophagic flux upon the treatment with AgNPs. The elongation and closure of autophagic vacuoles was also supported by upregulated Atg genes (Atg4, Atg3, Atg5) in A. baumannii infected cells after treatment with AgNP. Autophagic flux increased on treatment with PVP-AgNP as suggested by the rise in mcherryLC3B fluorescence in A549 cells treated with PVP-AgNP as compared to the GFP-LC3B of IVM-AgNP. This suggests that PVP-AgNP treatment more effectively promotes the elongation and maturation stages of autophagy by increasing autophagic flux. These results indicate that capped AgNPs have the efficiency to revert the incomplete autophagy induced by A. baumannii back to normal autophagic levels.

6.
Eur J Med Chem ; 279: 116833, 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39243454

ABSTRACT

The growing prevalence of MDR and XDR bacterial pathogens is posing a critical threat to global health. Traditional antibiotic development paths have encountered significant challenges and are drying up thus necessitating innovative approaches. Drug repurposing, which involves identifying new therapeutic applications for existing drugs, offers a promising alternative to combat resistant pathogens. By leveraging pre-existing safety and efficacy data, drug repurposing accelerates the development of new antimicrobial therapy regimes. This review explores the potential of repurposing existing FDA approved drugs against the ESKAPE and other clinically relevant bacterial pathogens and delves into the identification of suitable drug candidates, their mechanisms of action, and the potential for combination therapies. It also describes clinical trials and patent protection of repurposed drugs, offering perspectives on this evolving realm of therapeutic interventions against drug resistance.

7.
Microb Pathog ; 196: 106937, 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39293727

ABSTRACT

The spread of bacterial resistance has become a significant public health concern, resulting in increased healthcare costs, mortality, and morbidity. Phytochemicals such as Eugenol, the major component of Indian clove and cinnamon essential oils, have attracted attention due to their antimicrobial potential. Thus, this systematic review aims to analyze the existing literature on the antibacterial potential of Eugenol concerning its activity against biofilms, bacterial communication systems (quorum sensing - QS), and associated virulence factors. For this, four databases were systematically searched to retrieve articles published between 2010 and 2023. Fourteen articles were selected based on eligibility criteria and the evaluation of antibacterial activity through minimum inhibitory concentration (MIC) assays, biofilm studies, and assessment of virulence factors. The results revealed that Eugenol has the potential to act as an antimicrobial, antibiofilm, anti-virulence, and anti-QS agent against a variety of bacterial strains associated with chronic, dental, and foodborne infections, including resistant strains, particularly those in the ESKAPE group (Enterococcus spp., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) and clinical isolates. Furthermore, Eugenol effectively targets key genes involved in bacterial virulence regulation, biofilm, and QS, as supported by data from multiple assays and research techniques. This review suggests Eugenol's antibacterial activity against biofilm and virulence factors likely stems from its influence on different QS systems. Finally, Eugenol holds promise as a potential candidate for combating resistant bacterial infections, serving as an anti-biofilm agent in medical devices and hospital surfaces, as well as in the food industry, as a toothpaste additive, and as a molecule for the development of new therapeutic agents with the potential to inhibit bacterial virulence, QS systems and avoiding bacterial resistance.

8.
Front Microbiol ; 15: 1440658, 2024.
Article in English | MEDLINE | ID: mdl-39290512

ABSTRACT

Introduction: Bacterial infection and biofilm formation contribute to impaired healing in chronic diabetic wounds. Staphylococcus aureus and Pseudomonas aeruginosa are found in human diabetic wound biofilms. They may develop antibiotic resistance, increasing the urgency for alternative or complementary therapies. Diabetic wound healing may be improved with the use of biomedically engineered scaffolds, which can also serve as delivery systems for antibacterial compounds. Manuka honey is a potent antibacterial and wound care agent due to its high osmolarity, low pH, and constituents (such as methylglyoxal). Honey exhibits bacteriostatic and bactericidal effects, modulates the expression of biofilm forming genes, and restores antibiotic susceptibility in previously drug resistant pathogens. Methods: In this study, we created a dermal regeneration template (DRT) composed of polycaprolactone-gelatin (PCL-gelatin) and Manuka honey to retain honey in the wound and also provide a scaffold for tissue regeneration. Results and discussion: Soluble Manuka honey inhibited the planktonic and biofilm growth of both S. aureus (UWH3) and P. aeruginosa (PA14) co-cultures. Manuka honey embedded PCL-gelatin scaffolds did not exhibit bacteriostatic or bactericidal effects on cocultures of UHW3 and PA14; however, they promoted the expression of AgrA, a gene associated with dispersal of S. aureus biofilms.

9.
Prog Mol Biol Transl Sci ; 208: 19-41, 2024.
Article in English | MEDLINE | ID: mdl-39266183

ABSTRACT

Prokaryotic adaptive immune systems called CRISPR-Cas systems have transformed genome editing by allowing for precise genetic alterations through targeted DNA cleavage. This system comprises CRISPR-associated genes and repeat-spacer arrays, which generate RNA molecules that guide the cleavage of invading genetic material. CRISPR-Cas is classified into Class 1 (multi-subunit effectors) and Class 2 (single multi-domain effectors). Its applications span combating antimicrobial resistance (AMR), targeting antibiotic resistance genes (ARGs), resensitizing bacteria to antibiotics, and preventing horizontal gene transfer (HGT). CRISPR-Cas3, for example, effectively degrades plasmids carrying resistance genes, providing a precise method to disarm bacteria. In the context of ESKAPE pathogens, CRISPR technology can resensitize bacteria to antibiotics by targeting specific resistance genes. Furthermore, in tuberculosis (TB) research, CRISPR-based tools enhance diagnostic accuracy and facilitate precise genetic modifications for studying Mycobacterium tuberculosis. CRISPR-based diagnostics, leveraging Cas endonucleases' collateral cleavage activity, offer highly sensitive pathogen detection. These advancements underscore CRISPR's transformative potential in addressing AMR and enhancing infectious disease management.


Subject(s)
Bacterial Infections , CRISPR-Cas Systems , CRISPR-Cas Systems/genetics , Humans , Bacterial Infections/microbiology , Bacterial Infections/genetics , Gene Editing , Bacteria/genetics
10.
Infect Drug Resist ; 17: 3813-3823, 2024.
Article in English | MEDLINE | ID: mdl-39247758

ABSTRACT

Background: Antimicrobial resistance to ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp). remains a major challenge in hospital settings. Objective: This study aimed to determine the ESKAPE antimicrobial resistance patterns and associated factors with multi-drug resistance strains among hospitalized patients in a single tertiary care medical hospital in Palestine. Methods: A single-center retrospective cross-sectional study was conducted by reviewing patients' electronic medical records and laboratory results from November 1, 2021, to November 30, 2022, at the Palestine Medical Complex in Palestine. The study included patients aged > 18 years who had been infected with ESKAPE pathogens 48 hours after hospital admission. Results: This study included 231 patients, of whom 90.5% had MDR infections. In total, 331 clinical samples of ESKAPE pathogens were identified. A. baumannii was the most prevalent MDR pathogen (95.6%) with Carbapenem-resistant exceeding 95%, followed by K. pneumoniae (83.8%) with extended-spectrum cephalosporin resistance exceeding 90%, S. aureus (68.2) with 85% oxacillin-resistance, E. faecium (40%) with 20% vancomycin resistance, P. aeruginosa (22.6%) with 30% carbapenem resistance. Furthermore, emergent colistin resistance has been observed in A. baumannii, K. pneumoniae, and P. aerogenesis. Risk factors for MDR infection included age (p< 0.035), department (p< 0.001), and invasive procedures such as IUC (p< 0.001), CVC (p< 0.000), and MV (p< 0.008). Patients diagnosed with MDR bacteria had increased 30-day mortality (p< 0.001). Conclusion: The findings of this study show alarming MDR among hospitalized patients infected with ESKAPE pathogens, with resistance to first-line antimicrobial agents and emerging resistance to colistin, minimizing treatment options. Healthcare providers and the Ministry of Health must take steps, adopt policies to prevent antimicrobial resistance, adhere to infection control guidelines, implement antimicrobial stewardship programs to prevent and limit the growing health crisis, and support research to discover new treatment options.

11.
Acta Microbiol Immunol Hung ; 71(3): 211-219, 2024 Sep 18.
Article in English | MEDLINE | ID: mdl-39190489

ABSTRACT

Hospital acquired infections greatly affect recovery and survival in pediatric surgical patients. We evaluated prevalence and antimicrobial resistance of ESKAPE pathogens in neonates and infants subjected to cardiac surgery in a tertiary hospital in Central Kazakhstan between 2019 and 2023 (2,278 patients) using routine methods of microbiological detection. ESKAPE pathogens were found in 1,899 out of 2,957 samples (Staphylococcus aureus - 35.3%, Klebsiella pneumoniae - 27.8%, Acinetobacter baumannii - 14.5%, Pseudomonas aeruginosa - 12.4%, Enterobacter sp. - 8.8%, Enterococcus faecium - 1.2%). The total prevalence of ESKAPE increased significantly from 45.1 to 76.9% (P = 0.005) during the study period. The resistance significantly increased in methicillin-resistant S. aureus (MRSA, from 13.7 to 41.9%, P = 0.041) but decreased in carbapenem-resistant P. aeruginosa (from 64.3 to 37.7%, P = 0.037) and carbapenem-resistant A. baumannii (from 48.5 to 19.1%, P = 0.039). Gradual but non-significant changes were shown in third-generation cephalosporin resistant K. pneumoniae (from 63.6 to 45.2%) and carbapenem-resistant K. pneumoniae (from 0 to 8.3%). The relative prevalence of ESKAPE pathogens steadily increased in our pediatric cardiac surgery patients in 2019-2023. The most frequent were S. aureus, K. pneumoniae, and A. baumannii, with dramatically increasing tendencies for MRSA. Our results highlight the necessity for a well-designed infection control strategy and constant microbiological monitoring in pediatric cardiac surgery departments.


Subject(s)
Tertiary Care Centers , Humans , Kazakhstan/epidemiology , Tertiary Care Centers/statistics & numerical data , Infant , Infant, Newborn , Anti-Bacterial Agents/pharmacology , Female , Male , Cardiac Surgical Procedures , Prevalence , Cross Infection/microbiology , Cross Infection/epidemiology , Drug Resistance, Bacterial , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Klebsiella pneumoniae/isolation & purification , Klebsiella pneumoniae/drug effects , Bacteria/isolation & purification , Bacteria/classification , Bacteria/drug effects , Microbial Sensitivity Tests , Pseudomonas aeruginosa/isolation & purification , Pseudomonas aeruginosa/drug effects
12.
ACS Infect Dis ; 10(9): 3346-3357, 2024 Sep 13.
Article in English | MEDLINE | ID: mdl-39106475

ABSTRACT

The crystal structure of a previously reported antimicrobial RuII complex that targets bacterial DNA is presented. Studies utilizing clinical isolates of Gram-negative bacteria that cause catheter-associated urinary tract infection, (CA)UTI, in media that model urine and plasma reveal that good antimicrobial activity is maintained in all conditions tested. Experiments with a series of Staphylococcus aureus clinical isolates show that, unlike the majority of previously reported RuII-based antimicrobial leads, the compound retains its potent activity even in MRSA strains. Furthermore, experiments using bacteria in early exponential growth and at different pHs reveal that the compound also retains its activity across a range of conditions that are relevant to those encountered in clinical settings. Combinatorial studies involving cotreatment with conventional antibiotics or a previously reported analogous dinuclear RuII complex showed no antagonistic effects. In fact, although all combinations show distinct additive antibacterial activity, in one case, this effect approaches synergy. It was found that the Galleria Mellonella model organism infected with a multidrug resistant strain of the ESKAPE pathogen Acinetobacter baumannii could be successfully treated and totally cleared within 48 h after a single dose of the lead complex with no detectable deleterious effect to the host.


Subject(s)
Anti-Bacterial Agents , Microbial Sensitivity Tests , Ruthenium , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Ruthenium/chemistry , Ruthenium/pharmacology , Moths/drug effects , Moths/microbiology , Staphylococcus aureus/drug effects , Humans , Urinary Tract Infections/microbiology , Urinary Tract Infections/drug therapy , Coordination Complexes/pharmacology , Coordination Complexes/chemistry , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology
13.
Front Microbiol ; 15: 1447301, 2024.
Article in English | MEDLINE | ID: mdl-39171261

ABSTRACT

Introduction: This study investigated the interaction with membrane mimetic systems (LUVs), bacterial membranes, the CD spectra, and the bactericidal activity of two designed trematocine mutants, named Trem-HK and Trem-HSK. Mutants were constructed from the scaffold of Trematocine (Trem), a natural 22-amino acid AMP from the Antarctic fish Trematomus bernacchii, aiming to increase their positive charge. Methods: The selectivity of the designed AMPs towards bacterial membranes was improved compared to Trematocine, verified by their interaction with different LUVs and their membranolytic activity. Additionally, their α-helical conformation was not influenced by the amino acid substitutions. Our findings revealed a significant enhancement in antibacterial efficacy against ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae family) pathogens for both Trem-HK and Trem-HSK. Results: Firstly, we showed that the selectivity of the two new designed AMPs towards bacterial membranes was greatly improved compared to Trematocine, verifying their interaction with different LUVs and their membranolytic activity. We determined that their α-helical conformation was not influenced by the amino acid substitutions. We characterized the tested bacterial collection for resistance traits to different classes of antibiotics. The minimum inhibitory and bactericidal concentration (MIC and MBC) values of the ESKAPE collection were reduced by up to 80% compared to Trematocine. The bactericidal concentrations of Trematocine mutants showed important membranolytic action, evident by scanning electron microscopy, on all tested species. We further evaluated the cytotoxicity and hemolytic activity of the mutants. At 2.5 µM concentration, both mutants demonstrated low cytotoxicity and hemolysis, indicating selectivity towards bacterial cells. However, these effects increased at higher concentrations. Discussion: Assessment of in vivo toxicity using the Galleria mellonella model revealed no adverse effects in larvae treated with both mutants, even at concentrations up to 20 times higher than the lowest MIC observed for Acinetobacter baumannii, suggesting a high potential safety profile for the mutants. This study highlights the significant improvement in antibacterial efficacy achieved by increasing the positive charge of Trem-HK and Trem-HSK. This improvement was reached at the cost of reduced biocompatibility. Further research is necessary to optimize the balance between efficacy and safety for these promising AMPs.

14.
Water Res ; 263: 122200, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39111212

ABSTRACT

Prophages are prevalent among bacterial species, including strains carrying antibiotic resistance genes (ARGs). Prophage induction can be triggered by the SOS response to stressors, leading to cell lysis. In environments polluted by chemical stressors, ARGs and prophage co-harboring strains might pose an unknown risk of spreading ARGs through chemical pollutant-mediated prophage induction and subsequent cell lysis. In this study, we investigated the effects of common non-antibiotic water pollutants, triclosan and silver nanoparticles, on triggering prophage induction in clinical isolates carrying ARGs and the subsequent uptake of released ARGs by the naturally competent bacterium Acinetobacter baylyi. Our results demonstrate that both triclosan and silver nanoparticles, at environmentally relevant concentrations and those found in commercial products, significantly enhance prophage induction among various clinical isolates. Transmission electron microscopy imaging and plaque assays confirmed the production of infectious phage particles under non-antibiotic pollutants-mediated prophage induction. In addition, the rate of ARG transformation to A. baylyi significantly increased after the release of extracellular ARGs from prophage induction-mediated cell lysis. The mechanism of non-antibiotic pollutants-mediated prophage induction is primarily associated with excessive oxidative stress, which provokes the SOS response. Our findings offer insights into the role of non-antibiotic pollutants in promoting the dissemination of ARGs by triggering prophage induction.


Subject(s)
Prophages , Prophages/genetics , Acinetobacter/drug effects , Acinetobacter/genetics , Drug Resistance, Microbial/genetics , Triclosan/pharmacology , Drug Resistance, Bacterial/genetics , Anti-Bacterial Agents/pharmacology , Metal Nanoparticles , Silver/pharmacology
15.
Front Microbiol ; 15: 1428808, 2024.
Article in English | MEDLINE | ID: mdl-39135871

ABSTRACT

The accelerated rise in antimicrobial resistance (AMR) poses a significant global health risk, necessitating the exploration of alternative strategies to combat pathogenic infections. Biofilm-related infections that are unresponsive to standard antibiotics often require the use of higher-order antimicrobials with toxic side effects and the potential to disrupt the microbiome. Probiotic therapy, with its diverse benefits and inherent safety, is emerging as a promising approach to prevent and treat various infections, and as an alternative to antibiotic therapy. In this study, we isolated novel probiotic bacteria from the gut of domestic goats (Capra hircus) and evaluated their antimicrobial and anti-biofilm activities against the 'ESKAPE' group of pathogens. We performed comprehensive microbiological, biochemical, and molecular characterizations, including analysis of the 16S-rRNA gene V1-V3 region and the 16S-23S ISR region, on 20 caprine gut-derived lactic acid bacteria (LAB). Among these, six selected Lactobacillus isolates demonstrated substantial biofilm formation under anaerobic conditions and exhibited robust cell surface hydrophobicity and autoaggregation, and epithelial cell adhesion properties highlighting their superior enteric colonization capability. Notably, these Lactobacillus isolates exhibited broad-spectrum growth inhibitory and anti-biofilm properties against 'ESKAPE' pathogens. Additionally, the Lactobacillus isolates were susceptible to antibiotics listed by the European Food Safety Authority (EFSA) within the prescribed Minimum Inhibitory Concentration limits, suggesting their safety as feed additives. The remarkable probiotic characteristics exhibited by the caprine gut-derived Lactobacillus isolates in this study strongly endorse their potential as compelling alternatives to antibiotics and direct-fed microbial (DFM) feed supplements in the livestock industry, addressing the escalating need for antibiotic-free animal products.

17.
Microorganisms ; 12(8)2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39203434

ABSTRACT

Chronic wounds are becoming an increasing burden on healthcare services, as they have extended healing times and are susceptible to infection, with many failing to heal, which can lead ultimately to amputation. Due to the additional rise in antimicrobial resistance and emergence of difficult-to-treat Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. (ESKAPE pathogens), novel treatments will soon be required asides from traditional antibiotics. Many natural substances have been identified as having the potential to aid in both preventing infection and increasing the speed of wound closure processes. Manuka honey is already in some cases used as a topical treatment in the form of ointments, which in conjunction with dressings and fish skin grafts are an existing US Food and Drug Administration-approved treatment option. These existing treatment options indicate that fatty acids from fish oil and manuka honey are well tolerated by the body, and if the active components of the treatments were better understood, they could make valuable additions to topical treatment options. This review considers two prominent natural substances with established manufacturing and global distribution-marine based fatty acids (including their metabolites) and manuka honey-their function as antimicrobials and how they can aid in wound repair, two important aspects leading to resolution of chronic wounds.

18.
Pathogens ; 13(8)2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39204298

ABSTRACT

Far-ultraviolet C light, with a wavelength of 200-230 nm, has demonstrated broad-spectrum germicidal efficacy. However, due to increased interest in its use as an alternative antimicrobial, further knowledge about its fundamental bactericidal efficacy is required. This study had two objectives. Firstly, it investigated experimentally the Far-UVC dose-response of common bacteria suspended at various cell densities in transparent buffer, ensuring no influence from photosensitive suspending media. Increasing doses of Far-UVC were delivered to Enterococcus faecium, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus in PBS at 101, 102, 103, 105 and 107 CFU·mL-1, with surviving colony-forming units enumerated (n ≥ 3). Secondly, through a systematised literature review, this work sought to explore the impact of genus/species, Gram type, cell form, cell density and irradiance on dose-response. The screening of 483 publications was performed with 25 included in the study. Data for 30 species were collated, analysed and compared with the experimental results. Overall, Gram-positive species showed greater resilience to Far-UVC than Gram-negative; some inter-species and inter-genera differences in resilience were identified; endospores were more resilient than vegetative cells; the results suggested that inactivation efficiency may decrease as cell density increases; and no significant correlation was identified between irradiance and bactericidal dose effect. In conclusion, this study has shown Far-UVC light to be an effective decontamination tool against a vast range of bacterial vegetative cells and endospores.

19.
Microb Pathog ; 194: 106842, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39117012

ABSTRACT

ESKAPE pathogens, a notorious consortium comprising Enterococcusfaecium, Staphylococcusaureus, Klebsiellapneumoniae, Acinetobacterbaumannii, Pseudomonasaeruginosa, and Enterobacter species, pose formidable challenges in healthcare settings due to their multidrug-resistant nature. The increasing global cases of antimicrobial-resistant ESKAPE pathogens are closely related to their remarkable ability to form biofilms. Thus, understanding the unique mechanisms of antimicrobial resistance of ESKAPE pathogens and the innate resilience of biofilms against traditional antimicrobial agents is important for developing innovative strategies to establish effective control methods against them. This review offers a thorough analysis of biofilm dynamics, with a focus on the general mechanisms of biofilm formation, the significant contribution of persister cells in the resistance mechanisms, and the recurrence of biofilms in comparison to planktonic cells. Additionally, this review highlights the potential strategies of nanoparticles for managing biofilms in the ESKAPE group of pathogens. Nanoparticles, with their unique physicochemical properties, provide promising opportunities for disrupting biofilm structures and improving antimicrobial effectiveness. The review has explored interactions between nanoparticles and biofilms, covering a range of nanoparticle types such as metal, metal-oxide, surface-modified, and functionalized nanoparticles, along with organic nanoparticles and nanomaterials. The additional focus of this review also encompasses green synthesis techniques of nanoparticles that involve plant extract and supernatants from bacterial and fungal cultures as reducing agents. Furthermore, the use of nanocomposites and nano emulsions in biofilm management of ESKAPE is also discussed. To conclude, the review addresses the current obstacles and future outlooks in nanoparticle-based biofilm management, stressing the necessity for further research and development to fully exploit the potential of nanoparticles in addressing biofilm-related challenges.


Subject(s)
Anti-Bacterial Agents , Biofilms , Nanoparticles , Biofilms/drug effects , Biofilms/growth & development , Nanoparticles/chemistry , Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Humans , Drug Resistance, Multiple, Bacterial/drug effects
20.
Braz J Microbiol ; 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38985434

ABSTRACT

An Actinomycetia isolate, designated as PBR19, was derived from the rhizosphere soil of Pobitora Wildlife Sanctuary (PWS), Assam, India. The isolate, identified as Streptomyces sp., shares a sequence similarity of 93.96% with its nearest type strain, Streptomyces atrovirens. This finding indicates the potential classification of PBR19 as a new taxon within the Actinomycetota phylum. PBR19 displayed notable antibacterial action against some ESKAPE pathogens. The ethyl acetate extract of PBR19 (EtAc-PBR19) showed the lowest minimum inhibitory concentration (MIC) of ≥ 0.195 µg/mL against Acinetobacter baumannii ATCC BAA-1705. A lower MIC indicates higher potency against the tested pathogen. Scanning electron microscope (SEM) findings revealed significant changes in the cytoplasmic membrane structure of the pathogen. This suggests that the antibacterial activity may be linked to the disruption of the microbial membrane. The predominant chemical compound detected in the EtAc-PBR19 was identified as phenol, 3,5-bis(1,1-dimethylethyl), comprising 48.59% of the area percentage. Additionally, PBR19 was found to contain the type II polyketide synthases (PKS type II) gene associated with antibiotic synthesis. The predicted gene product of PKSII was identified as the macrolide antibiotic Megalomicin A. The taxonomic distinctiveness, potent antibacterial effects, and the presence of a gene associated with antibiotic synthesis suggest that PBR19 could be a valuable candidate for further exploration in drug development and synthetic biology. The study contributes to the broader understanding of microbial diversity and the potential for discovering bioactive compounds in less-explored environments.

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