Multidrug-resistant Bacteria Research Articles

Immunosenescence: How Aging Increases Susceptibility to Bacterial Infections and Virulence Factors.

The process of aging leads to a progressive decline in the immune system function, known as immunosenescence, which compromises both innate and adaptive responses. This includes impairments in phagocytosis and decreased production, activation, and function of T- and B-lymphocytes, among other effects. Bacteria exploit immunosenescence by using various virulence factors to evade the host's defenses, leading to severe and often life-threatening infections. This manuscript explores the complex relationship between immunosenescence and bacterial virulence, focusing on the underlying mechanisms that increase vulnerability to bacterial infections in the elderly. Additionally, it discusses how machine learning methods can provide accurate modeling of interactions between the weakened immune system and bacterial virulence mechanisms, guiding the development of personalized interventions. The development of vaccines, novel antibiotics, and antivirulence therapies for multidrug-resistant bacteria, as well as the investigation of potential immune-boosting therapies, are promising strategies in this field. Future research should focus on how machine learning approaches can be integrated with immunological, microbiological, and clinical data to develop personalized interventions that improve outcomes for bacterial infections in the growing elderly population.

Comparative Properties of Helical and Linear Amphipathicity of Peptides Composed of Arginine, Tryptophan, and Valine.

The persistence of antibiotic resistance has incited a strong interest in the discovery of agents with novel antimicrobial mechanisms. The direct killing of multidrug-resistant bacteria by cationic antimicrobial peptides (AMPs) underscores their importance in the fight against infections associated with antibiotic resistance. Despite a vast body of AMP literature demonstrating a plurality in structural classes, AMP engineering has been largely skewed toward peptides with idealized amphipathic helices (H-amphipathic). In contrast to helical amphipathicity, we designed a series of peptides that display the amphipathic motifs in the primary structure. We previously developed a rational framework for designing AMP libraries of H-amphipathic peptides consisting of Arg, Trp, and Val (H-RWV, with a confirmed helicity up to 88% in the presence of membrane lipids) tested against the most common MDR organisms. In this study, we re-engineered one of the series of the H-RWV peptides (8, 10, 12, 14, and 16 residues in length) to display the amphipathicity in the primary structure by side-by-side (linear) alignment of the cationic and hydrophobic residues into the 2 separate linear amphipathic (L-amphipathic) motifs. We compared the 2 series of peptides for antibacterial activity, red blood cell (RBC) lysis, killing and membrane-perturbation properties. The L-RWV peptides achieved the highest antibacterial activity at a minimum length of 12 residues (L-RWV12, minimum optimal length or MOL) with the lowest mean MIC of 3-4 µM, whereas the MOL for the H-RWV series was reached at 16 residues (H-RWV16). Overall, H-RWV16 displayed the lowest mean MIC at 2 µM but higher levels of RBC lysis (25-30%), while the L-RWV series displayed minor RBC lytic effects at the test concentrations. Interestingly, when the S. aureus strain SA719 was chosen because of its susceptibility to most of the peptides, none of the L-RWV peptides demonstrated a high level of membrane perturbation determined by propidium iodide incorporation measured by flow cytometry, with <50% PI incorporation for the L-RWV peptides. By contrast, most H-RWV peptides displayed almost up to 100% PI incorporation. The results suggest that membrane perturbation is not the primary killing mechanism of the L-amphipathic RWV peptides, in contrast to the H-RWV peptides. Taken together, the data indicate that both types of amphipathicity may provide different ideal pharmacological properties that deserve further investigation.

Microbiological studies on Escherichia coli and Klebsiella pneumoniae causing vaginal and urinary tract inflammation; prevalence, antibiotics-resistance and natural products susceptibility

Great efforts have been made for controlling multidrug-resistant bacteria (MDR). The antibacterial activity of natural products is an effective strategy due to its beneficial effects on human health. This study focused on the isolation, identification, studying the prevalence and the susceptibility of Escherichia coli and Klebsiella spp. to some natural products. After isolation, the isolates primarily identified using biochemical and API tests. Then, the antibiotic susceptibility test was done to reveal the most antibiotics resistant isolates before further identification of Escherichia coli and Klebsiella pneumoniae using phoA and gyrA genes, respectively. Furthermore, the sensitivity of the most antibiotics resistant isolates to apple cider vinegar (ACV), garlic oil (GO), coconut oil (CNO), tea tree oil (TTO), and lavender oil (LO) was estimated. All tested extracts especially ACV and TTO showed good antibacterial activity against MRD selected isolates. Statistical analysis indicated that there was significant difference in ACV and TTO antibacterial response between Escherichia coli and Klebsiella pneumoniae whereas there was no significant difference between natural products activity when tested against Escherichia coli and Klebsiella pneumoniae seperatly. GC-MS spectroscopy analysis revealed the most prominent active constituents present in tested ACV and TTO. Analyzing the 16S rRNA sequence confirmed the two most MRD pathogenic isolates that showed sensitivity to ACV and TTO were Escherichia coli MS1 and Klebsiella pneumoniae MS47, respectively. Essential oils tea tree and apple cider vinegar showed good antibacterial activities against antibiotics-resistant Escherichia coli and Klebsiella pneumoniae causing vaginal and urinary tract inflammation.

Differential MRGPRX2-dependent activation of human mast cells by polymyxins and octapeptins

The emergence of multi-drug resistant Gram-negative bacteria has led to renewed interest in the antimicrobial activity of polymyxins and novel polymyxin analogues (e.g. nonapeptides and octapeptin). In some individuals, clinically used polymyxins can cause acute hypersensitivity reactions through mast cell activation, with a recent study attributing this effect to activation of the MAS-related G protein-coupled receptor X2 (MRGPRX2). In the present study, HEK293 cells expressing human MRGPRX2 and the human mast cell line LAD2 were used to characterize the activity of the broader family of polymyxins. Octapeptin C4, polymyxin B and colistin produced concentration-dependent calcium mobilization, degranulation, and CCL-2 (MCP-1) release in LAD2 mast cells, with the former being highly potent. CRISPR-Cas9 knockdown of MRGPRX2 in LAD2 cells and a MRGPRX2 inverse agonist caused a significant reduction in calcium mobilization, degranulation, and CCL-2 release, demonstrating dependency on MRGPRX2 expression. In contrast, polymyxin nonapeptides were far less potent calcium mobilisers and failed to induce functional degranulation in LAD2 cells. Our results confirm that activation of mast cells induced by polymyxin-related antibiotics is MRGPRX2-dependent and reveal that octapeptin C4 might be more liable, whilst nonapeptides are less liable, to trigger immediate hypersensitivity reactions clinically. The mechanism underpinning the difference in MRGPRX2 activation between polymyxin-related antibiotics is important to better understand as it may help design new, safer polymyxins and guide the optimal clinical use of existing polymyxin drugs.

First report of carbapenems encoding multidrug-resistant gram-negative bacteria from a pediatric hospital in Gaza Strip, Palestine

BackgroundThe worldwide prevalence of multi-drug resistance (MDR) in Gram-negative bacteria (GNB), particularly related to extended-spectrum beta-lactamases (ESBLs) and carbapenemases, poses significant global public health and clinical challenges.ObjectivesTo characterize ESBL-producing Gram-negative bacilli, within a pediatric hospital in Gaza using whole genome sequencing (WGS).MethodsA total of 158 clinical isolates of Gram-negative bacilli were collected from Al-Nasser Pediatric Hospital. These isolates were tested for ESBL production using the double disk synergy test. The antibiotic susceptibility profile was determined using the Kirby Bauer method following the Clinical and Laboratory Standard Institute guidelines. Selected 15 phenotypically MDR isolates were whole-genome sequenced and characterized for their genome-based species identity and antibiotic resistance gene profile.ResultsOf the 158 isolates, 93 (58.9%) were positive for ESBL production. The frequency of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Proteus mirabilis, and Serratia marcescens was 50%, 22.7%, 22.7%, 1.8%, 1.2%, and 1.2% respectively. The prevalence of ESBL among urine, pus, blood, and sputum was 64%, 44%, 23%, and 63.6%, respectively. Chloramphenicol, Imipenem, and Meropenem were the most effective antibiotics against ESBL producers.In sequenced isolates, an average of six anti-microbial resistance (AMR) genes were noted per isolate, where one of them carried up to 13 antibiotic resistance genes. Carbapenem resistance genes such as blaKPC-2(6.6%), blaPDC-36/12 (6.6%), and blaPOM-1 (6.6%) were detected. All the sequenced E. coli isolates (n = 8) showed multiple resistance genes, mainly against β-lactamase (25.0%), aminoglycosides (37.5%), sulfonamides (37.5%), and genes conferring resistance to tetracyclines (25.0).ConclusionOur results showed a high prevalence of ESBL-producing GNB isolated from a pediatric hospital in the Gaza Strip. Various antibiotic resistance genes were identified, including those encoding ESBL and carbapenems. The results highlight the significant challenge posed by MDR in GNB and emphasize the need for effective antibiotic strategies. Given the high endemicity observed in various studies from Palestine, it is important to conduct clinical and molecular epidemiology research to identify risk factors, transmission patterns, and clinical outcomes associated with GNB strains that carry ESBL and carbapenem resistance genes.

A chitosan-modified tea tree oil self-nanoemulsion improves antibacterial effects in vivo and in vitro and promotes wound healing by influencing metabolic processes against multidrug-resistant bacterial infections

Infectious diseases, especially multidrug-resistant bacterial infections, have caused crises and majorly disrupted public health and economic stability worldwide. Many natural essential oils, especially tea tree oil, have potential to treat multidrug-resistant bacteria, such as H. pylori and P. aeruginosa. However, there are some problems need to be solved, such as poor stability upon light or oxygen exposure. Therefore, it is urgent to develop the ideal formation to tackle these difficulties. Herein, we reported the novel chitosan-modified self-nanoemulsion (TNE) encapsulating natural essential tea tree oil with strong antibacterial and stability characterize. In this study, we found that this self-nanoemulsion (size: 212 nm, PDI: 0.124, zeta potential: −20.5 mV, 6 % tea tree oil) not only had physical properties, good stability and tissue safety, but also had better antibacterial synergism (2–8 times) than that of water suspension against various multidrug-resistant bacterial (such as H. pylori, MRSA and P. aeruginosa). Additionally, TNE showed high antibacterial effectiveness in vivo, reduced inflammation, promoted ulcer healing after H. pylori infection and accelerated wound healing after P. aeruginosa infection. Importantly, this novel self-nanoemulsion can induce 274 protein down-regulated and 251 protein up-regulated, and disrupt H. pylori metabolic processes (glyoxylate, dicarboxylic acid, glutamate and tryptophan metabolism) and reduced its viability, leading to significant synergistic antibacterial effects. TNE is a potential treatment for skin wounds or ulcers caused by multidrug-resistant bacterial infections.

Particularities of Pyelonephritis With Multidrug-Resistant (MDR) Germs During Pregnancy: A Case-Control Study.

The aim of this study was to analyze the characteristics of pyelonephritis with multidrug-resistant (MDR) bacteria in pregnant women in comparison to pyelonephritis with multidrug-sensitive bacteria in this particular patient group. We conducted a retrospective study over a period of three years on a study group of 17 pregnant patients with pyelonephritis with MDR bacteria and on a control group of 52 pregnant patients with pyelonephritis with multidrug-sensitive bacteria. We analyzed the demographic data, the potential risk factors, aspects of the clinical picture, the incidence and type of bacteria involved, and their sensitivity spectrum. The patients in the study group had pyelonephritis on the right side (N=10, 58.83%), were in the second and third trimesters of pregnancy (N=16, 94.12%), and had a high percentage of anemia (N=9, 52.94%), as did the control group. Unlike the patients in the control group, the patients in the study group had a higher incidence of antibiotic treatment (N=17,100% vs. N=14, 29.92%, p<0.001), previous urological surgery, especially ureteral catheterization with insertion of double-J catheters (N=9, 52.94% vs. N=9, 17.30%, p=0.003), and an increased incidence of urosepsis on admission (N=11, 64.70% vs. N=11, 21.15%, p<0.001). E. coli (N=8, 47.05% vs. N=28, 53.85%, p=0.626) and Klebsiella pn. (N=5, 29.41% vs. N=12, 23.07%, p=0.598)were predominant in both study groups. Also, the hospitalization days were significantly higher in the study group compared with the control group (N=7.38±2,91 vs. N=5.02±1,87, p=0.002). The spectrum of microbial resistance was increased in favor of the study group for all antibiotics tested, with the exception of ampicillin, where resistance was increased in both groups. The Gram-negative bacteria responsible for the pyelonephritis in both groups retained 100% sensitivity to carbapenems and piperacillin/tazobactam. Pregnant women in the second and third trimesters of pregnancy who have undergone right-sided double-J catheter insertion during pregnancy and/or who have received antibiotic treatment in the past are at increased risk for pyelonephritis with MDR. E. coli and Klebsiella pn.,bacteria are most commonly involved and maintain susceptibility to carbapenems and reserve penicillins.

Antimicrobial Peptides Derived from Bacteria: Classification, Sources, and Mechanism of Action against Multidrug-Resistant Bacteria

Antimicrobial peptides (AMPs) are short, usually cationic peptides with an amphiphilic structure, which allows them to easily bind and interact with the cellular membranes of viruses, bacteria, fungi, and other pathogens. Bacterial AMPs, or bacteriocins, can be produced from Gram-negative and Gram-positive bacteria via ribosomal synthesis to eliminate competing organisms. Bacterial AMPs are vital in addressing the increasing antibiotic resistance of various pathogens, potentially serving as an alternative to ineffective antibiotics. Bacteriocins have a narrow spectrum of action, making them highly specific antibacterial compounds that target particular bacterial pathogens. This review covers the two main groups of bacteriocins produced by Gram-negative and Gram-positive bacteria, their modes of action, classification, sources of positive effects they can play on the human body, and their limitations and future perspectives as an alternative to antibiotics.

Risk factors for multidrug-resistant bacteria in critically ill children and MDR score development.

Antimicrobial resistance and healthcare-associated infections (HAIs) are major health concerns in the pediatric intensive care unit (PICU). Device-associated HAIs (DA-HAIs) produced by multidrug-resistant (MDR) bacteria are especially worrying, as they can lead to an inappropriate empirical antibiotic therapy, worsened outcomes and increased mortality. The MDR score was designed to enable the prompt identification of patients at high risk of developing an MDR infection. This was a single-center, prospective, observational study, conducted between January 2015 and December 2022, including PICU patients with a microbiologically confirmed DA-HAI. Demographic, clinical characteristics and outcomes were compared between patients with a DA-HAI caused by MDR and non-MDR-associated DA-HAI, and a risk score for multi-resistance was designed. In total, 257 DA-HAI cases were included, 86 (33.46%) caused by an MDR microbe. In the univariate analysis, comorbidity (p = 0.002), previous MDR colonization (p < 0.001), previous surgery (p = 0.018), and previous antibiotic therapy (p = 0.009) were more frequent among MDR-associated DA-HAI (MDR DA-HAI). In addition, days from device insertion to infection and from PICU admission (p < 0.005) to infection were longer in patients with MDR. In the multivariate analysis, previous comorbidity (OR 2.201), previous MDR colonization (OR 5.149), and PICU length of stay longer than 9days (OR 1.782) were independently associated with MDR-DA-HAI. Using these three independent risk factors for MDR, a risk score was created: the MDR score. Three risk groups were obtained: low risk (0-2 points), intermediate risk (3-7 points), and high risk (8-12 points). Seventy-one patients with MDR-DA-HAI (82.6%) were classified in the intermediate or high-risk group, with a global sensitivity of 82.6%. The specificity in the high-risk group was 91.8%, and 81.0% of patients who were stratified into the low-risk group had non-MDR-associated infections, so they were correctly classified. Conclusions: The MDR score can be a useful tool to stratify patients in risk groups for MDR-DA-HAI. It may help to guide the choice of empirical therapy, leading to early optimization and avoiding delays in establishing appropriate treatment. This study reinforces the importance of stratifying patients based on their individual risk profile for MDR infection.

Phage-liposome nanoconjugates for orthopedic biofilm eradication

Infection by multidrug-resistant (MDR) bacteria has become one of the biggest threats to public health worldwide. One reason for the difficulty in treatment is the lack of proper delivery strategies into MDR bacterial biofilms, where the thick extracellular polymeric substance (EPS) layer impedes the penetration of antibiotics and nanoparticles. Here, we propose a novel bioactive nanoconjugate of drug-loaded liposomes and bacteriophages for targeted eradication of the MDR biofilms in orthopedic infections. Phage Sb-1, which has the ability to degrade EPS, was conjugated with antibiotic-loaded liposomes. Upon encountering the biofilm, phage Sb-1 degrades the EPS structure, thereby increasing the sensitivity of bacteria to antibiotics and allowing the antibiotics to penetrate deeply into the biofilm. As a result, effective removal of MDR bacterial biofilm was achieved with low dose of antibiotics, which was proved in this study by both in vitro and in vivo investigations. Notably, in the rat prosthetic joint infection (PJI) model, we found that the liposome-phage nanoconjugates could effectively decrease the bacterial load in the infected area and significantly promote osteomyelitis recovery. It is therefore believed that the conjugation of bacteriophage and liposomes could open new possibilities for the treatment of orthopedic infections, possibly other infections in the deep tissues.

Simulation-Guided Molecular Modeling of Nisin and Lipid II Assembly and Membrane Pore Formation.

The lantibiotic pore-forming peptide nisin is a promising candidate in the fight against multidrug-resistant bacteria due to its unique structure, which allows it to disrupt bacteria in two distinct ways─Lipid II trafficking and transmembrane pore formation. However, exactly how nisin and Lipid II assemble into oligomeric pore structures in the bacterial membrane is not known. Spontaneous peptide assembly into pores is difficult to observe in even the very long-time scale molecular dynamics (MD) simulations. In this study, we adopted an MD-guided modeling approach to investigate the nisin-nisin and nisin-Lipid II associations in the membrane environment. Through extensive microsecond-time scale all-atom MD simulations, we established that nisin monomers dimerize by forming β-sheets in a POPE:POPG lipid bilayer and oligomerize further to form stable transmembrane channels. We determined that these nisin dimers use Lipid II as a dimer interface to incur enhanced stability. Our results provide a clearer understanding of the self-assembly of nisin monomers within the membrane and insights into the role of Lipid II in the structural integrity of oligomeric structures.

Oleanolic acid derivatives against drug-resistant bacteria and fungi by multi-targets to avoid drug resistance

Mixed infections caused by drug-resistant bacteria and fungi pose a severe threat to human health, and multi-target drugs may provide an effective approach to combat drug-resistant pathogens. Therefore, this study aimed to investigate the efficacies of some oleanolic acid (OA) derivatives against multidrug-resistant (MDR) bacteria and fungi using in vitro and in vivo experiments. Novel amphiphilic OA derivatives were designed and optimised, in which compounds G1 and J1 exhibited effective antimicrobial activity (MICs = 1–2 μg/mL), high selectivity against MDR strains, rapid bactericidal activity, and good predictive pharmacokinetics. Mechanistically, both compounds prevented drug resistance by disrupting the bacterial cell membrane, inserting into the DNA, and binding to DNA gyrase. Additionally, J1 reduced microbial count in a mouse MRSA skin infection model and accelerated wound healing much better than vancomycin. Conclusively, this study presents a new class of potential drugs for resistant bacteria and fungi.

Epidemiology of Infections Caused by ESBL-Producing Enterobacteriaceae and Antibiotic Resistance Profile of Strains Isolated at Meknes-Based Moulay Ismail Military Hospital: A Retrospective Study from January 2018 to December 2020

Introduction: Infections caused by ESBL-producing Enterobacteriaceae (ESBL-PE) pose a major public health challenge. In addition to their widespread presence and growing resistance to several categories of antibiotics, the medical management of these bacteria becomes intricate, potentially resulting in a therapeutic impasse. Our study's goal is to examine the regional epidemiological characteristics of ESBL-PE infections and present a current assessment of their antibiotic resistance. Methods: The retrospective investigation undertaken at the bacteriology laboratory of the Meknes-based Moulay Ismail Military Hospital, covering a period of three years (January 2018 to March 2021), specifically examines the isolates of ESBL-PE. Results: Among the 2596 strains of Enterobacteriaceae described, 16.4% were found to produce ESBL, with E. coli being accountable for 63.6% of these strains. 85.1% of these ESBL-PE were isolated from urine samples. Surgical services were the largest source of these ESBL-PE (54.3%), followed by the emergency department (22%), medical services (14.5%), and intensive care unit (9.2%). The antibiotic resistance of these ESBL-PE has been studied and found to be high for gentamicin (63%), tobramycin (66%), cotrimoxazole (85%), and ciprofloxacin (91%). Only 7% exhibited good sensitivity to amikacin, 4% to imipenem, and 5% to fosfomycin. Conclusion: The advent of ESBL-PE in our institution is a big challenge. To limit the use of carbapenems and prevent the spread of strains causing carbapenemases, other kinds of antibiotics can be utilized. The partnership between clinicians and the bacteriology laboratory is vital for efficiently preventing and monitoring the spread of these multidrug-resistant bacteria.

Whole-genome sequencing of Klebsiella pneumoniae MDR circulating in a pediatric hospital setting: a comprehensive genome analysis of isolates from Guayaquil, Ecuador

BackgroundKlebsiella pneumoniae is the major cause of nosocomial infections worldwide and is related to a worsening increase in Multidrug-Resistant Bacteria (MDR) and virulence genes that seriously affect immunosuppressed patients, long-stay intensive care patients, elderly individuals, and children. Whole-Genome Sequencing (WGS) has resulted in a useful strategy for characterizing the genomic components of clinically important bacteria, such as K. pneumoniae, enabling them to monitor genetic changes and understand transmission, highlighting the risk of dissemination of resistance and virulence associated genes in hospitals. In this study, we report on WGS 14 clinical isolates of K. pneumoniae from a pediatric hospital biobank of Guayaquil, Ecuador.ResultsThe main findings revealed pronounced genetic heterogeneity among the isolates. Multilocus sequencing type ST45 was the predominant lineage among non-KPC isolates, whereas ST629 was found more frequently among KPC isolates. Phylogenetic analysis suggested local transmission dynamics. Comparative genomic analysis revealed a core set of 3511 conserved genes and an open pangenome in neonatal isolates. The diversity of MLSTs and capsular types, and the high genetic diversity among these isolates indicate high intraspecific variability. In terms of virulence factors, we identified genes associated with adherence, biofilm formation, immune evasion, secretion systems, multidrug efflux pump transporters, and a notably high number of genes related to iron uptake. A large number of these genes were detected in the ST45 isolate, whereas iron uptake yersiniabactin genes were found exclusively in the non-KPC isolates. We observed high resistance to commonly used antibiotics and determined that these isolates exhibited multidrug resistance including β-lactams, aminoglycosides, fluoroquinolones, quinolones, trimetropins, fosfomycin and macrolides; additionally, resistance-associated point mutations and cross-resistance genes were identified in all the isolates. We also report the first K. pneumoniae KPC-3 gene producers in Ecuador.ConclusionsOur WGS results for clinical isolates highlight the importance of MDR in neonatal K. pneumoniae infections and their genetic diversity. WGS will be an imperative strategy for the surveillance of K. pneumoniae in Ecuador, and will contribute to identifying effective treatment strategies for K. pneumoniae infections in critical units in patients at stratified risk.

Dietary zinc supplementation inhibits bacterial plasmid conjugation in vitro by regulating plasmid replication (rep) and transfer (tra) genes.

Humans use dietary supplements for several intended effects, such as supplementing malnutrition. While these compounds have been developed for host end benefits, their ancillary impact on the gut microbiota remains unclear. The human gut has been proposed as a reservoir for the prevalent lateral transfer of antimicrobial resistance and virulence genes in bacteria through plasmid conjugation. Here, we studied the effect of dietary zinc supplements on the incidence of plasmid conjugation in vitro. Supplement effects were analyzed through standardized broth conjugation assays. The avian pathogenic Escherichia coli (APEC) strain APEC-O2-211 was a donor of the multidrug resistance plasmid pAPEC-O2-211A-ColV, and the human commensal isolate E. coli HS-4 was the plasmid-free recipient. Bacterial strains were standardized and mixed 1:1 and supplemented 1:10 with water, or zinc derived from either commercial zinc supplements or zinc gluconate reagent at varying concentrations. We observed a significant reduction in donors, recipients, and transconjugant populations in conjugations supplemented with zinc, with a dose-dependent relationship. Additionally, we observed a significant reduction (P < 0.05) in log conjugation efficiency in zinc-treated reactions. Upregulation of the mRNA for the plasmid replication initiation gene repA and the subset of transfer genes M, J, E, K, B, P, C, W, U, N, F, Q, D, I, and X was observed. Furthermore, we observed a downregulation of the conjugal propilin gene traA and the entry exclusion gene traS. This study demonstrates the effect of dietary zinc supplements on the conjugal transfer of a multidrug resistance plasmid between pathogenic and commensal bacteria during in vitro conditions.IMPORTANCEThis study identifies dietary zinc supplementation as a potential novel intervention for mitigating the emergence of multidrug resistance in bacteria, thus preventing antibiotic treatment failure and death in patients and animals. Further studies are required to determine the applicability of this approach in an in vivo model.

Prevalence and impact of multidrug-resistant bacteria in solid cancer patients with bloodstream infection: a 25-year trend analysis.

Multidrug-resistant (MDR) bacteria pose a global public health threat as they are more challenging to treat, and they are on the rise. Solid cancer patients are often immunocompromised due to their disease and cancer treatments, making them more susceptible to infections. Understanding the changes and trends in bloodstream infections in solid cancer patients is crucial, to help physicians make informed decisions about appropriate antibiotic therapies, manage infections in this vulnerable population, and prevent infection. Solid cancer patients often require intensive and prolonged treatments, including surgery, chemotherapy, and radiation therapy. Infections can complicate these treatments, leading to treatment delays, increased healthcare costs, and poorer patient outcomes. Investigating new strategies to combat MDR infections and researching novel antibiotics in these patients is of paramount importance to avoid these negative impacts.

Synergistic efficacy of ZnO quantum dots, Ag NPs, and nitazoxanide composite against multidrug-resistant human pathogens as new trend of revolutionizing antimicrobial treatment

Antibiotic resistance is currently becoming a more serious threat to global health, especially in severe nosocomial infections treatment by multidrug-resistant bacteria. This research provides a new way of synergizing green-synthesis for zinc oxide quantum dots (ZnO-QDs with hexagonal crystals) that are 7 nm in diameter and zero-valent Ag cubic crystals that are 67 nm in size embedded with nitazoxanide substrate (NAZ). Instrumental characterization like SEM, TEM, EDAX, and FT-IR and comprehensive antimicrobial studies were conducted to study the incorporation behavior of composites based on Ag NPs/ZnO QDs/NAZ. This combination has not been hitherto addressed anywhere else in the published literature, as well as commercial viability. In this context, we have precisely tuned nanoparticle to nitazoxanide ratio for designing the formulation demonstrating potent activity against MDR infections. By employing nitazoxanide as a scaffold and careful decoration thereof antimicrobial potency has been unlocked overriding conventional therapies. In addition, Ag NPs/ZnO-QDs/nitazoxanide (G6) formula exhibited a therapeutic efficacy span of 96.15 ± 1.68% to 99.57 ± 0.20% against MDR human infections post 48 h incubation; a breakthrough in therapeutic efficacy levels has been achieved by our method. Accordingly, ZnO QDs/Ag NPs/NAZ composite offered potential multidrug resistant human pathogens as a new trend of revolutionizing antimicrobial treatment.Graphical abstractSchematic diagram of synthesis routev ZnO quantum dots/Ag NPs/Nitazoxanide Triumphs composite NPs.

Electrically conductive and antimicrobial Pluronic-based hydrogels

Electrically conductive hydrogels (ECHs) combine the electrical properties of conductive materials with the unique features of hydrogels. They are attractive for various biomedical applications due to their smart response to electrical fields. Owing to their distinctive properties, such as biocompatibility, thermosensitivity and self-assembling behaviour, Pluronics can be adopted for the generation of hydrogels for biomedical applications. Here, innovative self-assembling ECHs holding antimicrobial properties for biomedical applications are developed, providing a full characterization of their macroscopic and microscopic properties. The rheological, morphological, and structural properties of Pluronic F68 (PF68) in the presence of conductive poly(3,4-ethylenedioxythiophene):poly-(styrenesulfonate) (PEDOT:PSS) are studied to optimize the synthesis of novel biocompatible and electrically conductive hydrogels. The addition of silver (Ag) flakes to the aqueous samples of PF68/PEDOT:PSS is used to further enhance the systems electrical conductivity and antimicrobial potency. Aqueous optimal samples with 45 wt% PF68 and different PEDOT:PSS/silver contents are investigated by means of experimental rheology and small-angle X-ray scattering (SAXS), to unveil the influence of both PEDOT:PSS and silver on the phase diagram, macroscopic flow properties, and morphology of the Pluronic-based systems.The presence of PEDOT:PSS and silver flakes endows Pluronic systems with high conductive properties, while preserving the same self-assembly features of PF68 in water. Moreover, the functionalisation with silver flakes confers antimicrobial properties to the ECHs, as demonstrated by growth inhibition of the multi-drug resistant bacterium Staphylococcus aureus.The use of PF68 in this work provides a novel route for the synthesis of innovative ECHs, whose functionalities such as self-assembling behaviour, biocompatibility, conductivity, and bioactivity may inspire future avenues in the biomedical field.

Whole genome analysis of multidrug-resistant Escherichia coli isolate collected from drinking water in Armenia revealed the plasmid-borne mcr-1.1-mediated colistin resistance.

Evolutionary patterns of Escherichia coli show that they usually develop into highly pathogenic forms by acquiring fitness advantages such as antimicrobial resistance (AMR) and various virulence factors through horizontal gene transfer mediated by mobile elements. This has led to high prevalence of multidrug-resistant (MDR) strains, which highlights the relevancy of enhanced surveillance to monitor and prevent transmission of the MDR bacteria to human and animal populations. However, the limited number of reports regarding the whole genome sequencing (WGS) investigation of MDR E. coli strains isolated from drinking water and harboring mcr genes hampers the adoption of a comprehensive approach to address the relationship between environmental E. coli populations and human and veterinary infections. Our results highlight the relevance of analyzing the environment, especially water, as a part of the surveillance programs to understand the origins and dissemination of antimicrobial resistance within the One Health concept.

Antibiotic resistant bacteria in goat meat and hygienic practices among retail stores in Nashville, Tennessee

This study explores into the levels of coliform contamination, prevalence of antibiotic-resistant bacteria, and the hygienic practices in goat meat retail stores. Goat meat from 10 retail stores was analyzed for E. coli, Salmonella, and S. aureus using serological and PCR methods. Antimicrobial susceptibility testing was performed using the Kirby-Bauer disk diffusion method. Data on hygienic practices were collected through a structured observational questionnaire. Pearson’s correlation analysis was also employed to establish the relationship between hygienic practices and coliform loads. The average coliform loads on goat meat ranged between 0.88–5.04 log10 cfu/g. Our results revealed that 52% of examined goat meat was deemed unacceptable (&amp;gt;3.30 log10 CFU/g). The overall level of good meat handling practices among meat handlers in our study was 45.75%. Further, the study establishes a significant correlation between the level of food safety practices and coliform load. Hence, stores with higher hygienic practice scores exhibited lower coliform loads. The prevalence of S. aureus (44%) in goat meat was significantly higher (p &amp;lt; 0.05) as compared to E. coli (29%), and Salmonella spp. (20%). E. coli isolates displayed the highest resistance to penicillin (31.2%), Salmonella spp. to oxytetracycline (13.9%), and S. aureus to ampicillin (29.0%). Resistance was observed across selected antibiotic classes, particularly in beta-lactams and tetracyclines, with penicillin (78.5%) and oxytetracycline (64.5%) exhibiting notable resistance. Cephalosporin resistance was noted, with 48.4 and 33.3% of isolates showing resistance to cephalothin and cefpodoxime, respectively. Bacterial isolates also demonstrated resistance to phenicol antibiotics, including chloramphenicol (9.7%) and florfenicol (16.1%), respectively. Approximately 44.1% of bacterial isolates displayed multidrug resistance and MAR index ranged from 0.25 to 0.75. The study’s findings reveal heightened levels of coliform contamination, the presence of pathogenic and multidrug-resistant bacteria in goat meat, and suboptimal meat handling practices in retail stores. The significance of improving food safety practices in retail settings is emphasized to ensure the safety of goat meat, a matter of increasing importance due to its growing demand globally.