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Frontiers in Cellular and Infection... 2024The dissemination of antibiotic resistance in poses a significant threat to public health worldwide. This review provides a comprehensive update on the diverse... (Review)
Review
The dissemination of antibiotic resistance in poses a significant threat to public health worldwide. This review provides a comprehensive update on the diverse mechanisms employed by in developing resistance to antibiotics. We primarily focus on pathotypes of (e.g., uropathogenic ) and investigate the genetic determinants and molecular pathways that confer resistance, shedding light on both well-characterized and recently discovered mechanisms. The most prevalent mechanism continues to be the acquisition of resistance genes through horizontal gene transfer, facilitated by mobile genetic elements such as plasmids and transposons. We discuss the role of extended-spectrum -lactamases (ESBLs) and carbapenemases in conferring resistance to -lactam antibiotics, which remain vital in clinical practice. The review covers the key resistant mechanisms, including: 1) Efflux pumps and porin mutations that mediate resistance to a broad spectrum of antibiotics, including fluoroquinolones and aminoglycosides; 2) adaptive strategies employed by , including biofilm formation, persister cell formation, and the activation of stress response systems, to withstand antibiotic pressure; and 3) the role of regulatory systems in coordinating resistance mechanisms, providing insights into potential targets for therapeutic interventions. Understanding the intricate network of antibiotic resistance mechanisms in is crucial for the development of effective strategies to combat this growing public health crisis. By clarifying these mechanisms, we aim to pave the way for the design of innovative therapeutic approaches and the implementation of prudent antibiotic stewardship practices to preserve the efficacy of current antibiotics and ensure a sustainable future for healthcare.
Topics: Humans; Escherichia coli; Escherichia coli Infections; Microbial Sensitivity Tests; Anti-Bacterial Agents; beta-Lactamases; Drug Resistance, Microbial
PubMed: 38638826
DOI: 10.3389/fcimb.2024.1387497 -
Proceedings. Biological Sciences Sep 2023Antimicrobial resistance (AMR) is a critical global health threat, and drivers of the emergence of novel strains of antibiotic-resistant bacteria in humans are poorly...
Antimicrobial resistance (AMR) is a critical global health threat, and drivers of the emergence of novel strains of antibiotic-resistant bacteria in humans are poorly understood at the global scale. We examined correlates of AMR emergence in humans using global data on the origins of novel strains of AMR bacteria from 2006 to 2017, human and livestock antibiotic use, country economic activity and reporting bias indicators. We found that AMR emergence is positively correlated with antibiotic consumption in humans. However, the relationship between AMR emergence and antibiotic consumption in livestock is modified by gross domestic product (GDP), with only higher GDP countries showing a slight positive association, a finding that differs from previous studies on the drivers of AMR prevalence. We also found that human travel may play a role in AMR emergence, likely driving the spread of novel AMR strains into countries where they are subsequently detected for the first time. Finally, we used our model to generate a country-level map of the global distribution of predicted AMR emergence risk, and compared these findings against reported AMR emergence to identify gaps in surveillance that can be used to direct prevention and intervention policies.
Topics: Humans; Animals; Anti-Bacterial Agents; Drug Resistance, Bacterial; Livestock; Travel
PubMed: 37727084
DOI: 10.1098/rspb.2023.1085 -
The ISME Journal Jan 2024Antimicrobial resistance is a major threat for public health. Plasmids play a critical role in the spread of antimicrobial resistance via horizontal gene transfer...
Antimicrobial resistance is a major threat for public health. Plasmids play a critical role in the spread of antimicrobial resistance via horizontal gene transfer between bacterial species. However, it remains unclear how plasmids originally recruit and assemble various antibiotic resistance genes (ARGs). Here, we track ARG recruitment and assembly in clinically relevant plasmids by combining a systematic analysis of 2420 complete plasmid genomes and experimental validation. Results showed that ARG transfer across plasmids is prevalent, and 87% ARGs were observed to potentially transfer among various plasmids among 8229 plasmid-borne ARGs. Interestingly, recruitment and assembly of ARGs occur mostly among compatible plasmids within the same bacterial cell, with over 88% of ARG transfers occurring between compatible plasmids. Integron and insertion sequences drive the ongoing ARG acquisition by plasmids, especially in which IS26 facilitates 63.1% of ARG transfer events among plasmids. In vitro experiment validated the important role of IS26 involved in transferring gentamicin resistance gene aacC1 between compatible plasmids. Network analysis showed four beta-lactam genes (blaTEM-1, blaNDM-4, blaKPC-2, and blaSHV-1) shuffling among 1029 plasmids and 45 clinical pathogens, suggesting that clinically alarming ARGs transferred accelerate the propagation of antibiotic resistance in clinical pathogens. ARGs in plasmids are also able to transmit across clinical and environmental boundaries, in terms of the high-sequence similarities of plasmid-borne ARGs between clinical and environmental plasmids. This study demonstrated that inter-plasmid ARG transfer is a universal mechanism for plasmid to recruit various ARGs, thus advancing our understanding of the emergence of multidrug-resistant plasmids.
Topics: Anti-Bacterial Agents; Plasmids; Drug Resistance, Microbial; Bacteria; Genes, Bacterial; Gene Transfer, Horizontal; Drug Resistance, Bacterial
PubMed: 38366209
DOI: 10.1093/ismejo/wrad032 -
Journal of Hazardous Materials Jun 2024Aquatic microplastics (MPs) act as reservoirs for microbial communities, fostering the formation of a mobile resistome encompassing diverse antibiotic (ARGs) and...
Aquatic microplastics (MPs) act as reservoirs for microbial communities, fostering the formation of a mobile resistome encompassing diverse antibiotic (ARGs) and biocide/metal resistance genes (BMRGs), and mobile genetic elements (MGEs). This collective genetic repertoire, referred to as the "plastiome," can potentially perpetuate environmental antimicrobial resistance (AMR). Our study examining two Japanese rivers near Tokyo revealed that waterborne MPs are primarily composed of polyethylene and polypropylene fibers and sheets of diverse origin. Clinically important genera like Exiguobacterium and Eubacterium were notably enriched on MPs. Metagenomic analysis uncovered a 3.46-fold higher enrichment of ARGs on MPs than those in water, with multidrug resistance genes (MDRGs) and BMRGs prevailing, particularly within MPs. Specific ARG and BMRG subtypes linked to resistance to vancomycin, beta-lactams, biocides, arsenic, and mercury showed selective enrichment on MPs. Network analysis revealed intense associations between host genera with ARGs, BMRGs, and MGEs on MPs, emphasizing their role in coselection. In contrast, river water exhibited weaker associations. This study underscores the complex interactions shaping the mobile plastiome in aquatic environments and emphasizes the global imperative for research to comprehend and effectively control AMR within the One Health framework.
Topics: Rivers; Microplastics; Anti-Bacterial Agents; Water Pollutants, Chemical; Bacteria; Water Microbiology; Interspersed Repetitive Sequences; Genes, Bacterial; Drug Resistance, Bacterial; Disinfectants; Microbiota; Drug Resistance, Microbial
PubMed: 38678707
DOI: 10.1016/j.jhazmat.2024.134353 -
Microbiology Spectrum Dec 2023Antibiotic resistance and tolerance are substantial healthcare-related problems, hampering effective treatment of bacterial infections. Mutations in the...
Antibiotic resistance and tolerance are substantial healthcare-related problems, hampering effective treatment of bacterial infections. Mutations in the phosphodiesterase GdpP, which degrades cyclic di-3', 5'-adenosine monophosphate (c-di-AMP), have recently been associated with resistance to beta-lactam antibiotics in clinical isolates. In this study, we show that high c-di-AMP levels decreased the cell size and increased the cell wall thickness in mutant strains. As a consequence, an increase in resistance to cell wall targeting antibiotics, such as oxacillin and fosfomycin as well as in tolerance to ceftaroline, a cephalosporine used to treat methicillin-resistant infections, was observed. These findings underline the importance of investigating the role of c-di-AMP in the development of tolerance and resistance to antibiotics in order to optimize treatment in the clinical setting.
Topics: Humans; Staphylococcus aureus; Methicillin-Resistant Staphylococcus aureus; Anti-Bacterial Agents; Staphylococcal Infections; Cell Wall; Methicillin Resistance; Oxidative Stress; Bacterial Proteins; Microbial Sensitivity Tests
PubMed: 37948390
DOI: 10.1128/spectrum.02788-23 -
Microbial Biotechnology Mar 2024In the relentless battle for human health, the proliferation of antibiotic-resistant bacteria has emerged as an impending catastrophe of unprecedented magnitude,...
In the relentless battle for human health, the proliferation of antibiotic-resistant bacteria has emerged as an impending catastrophe of unprecedented magnitude, potentially driving humanity towards the brink of an unparalleled healthcare crisis. The unyielding advance of antibiotic resistance looms as the foremost threat of the 21st century in clinical, agricultural and environmental arenas. Antibiotic resistance is projected to be the genesis of the next global pandemic, with grim estimations of tens of millions of lives lost annually by 2050. Amidst this impending calamity, our capacity to unearth novel antibiotics has languished, with the past four decades marred by a disheartening 'antibiotic discovery void'. With nearly 80% of our current antibiotics originating from natural or semi-synthetic sources, our responsibility is to cast our investigative nets into uncharted ecological niches teeming with microbial strife, the so-called 'microbial oases of interactions'. Within these oases of interactions, where microorganisms intensively compete for space and nutrients, a dynamic and ever-evolving microbial 'arms race' is constantly in place. Such a continuous cycle of adaptation and counter-adaptation is a fundamental aspect of microbial ecology and evolution, as well as the secrets to unique, undiscovered antibiotics, our last bastion against the relentless tide of resistance. In this context, it is imperative to invest in research to explore the competitive realms, like the plant rhizosphere, biological soil crusts, deep sea hydrothermal vents, marine snow and the most modern plastisphere, in which competitive interactions are at the base of the microorganisms' struggle for survival and dominance in their ecosystems: identify novel antibiotic by targeting microbial oases of interactions could represent a 'missing piece of the puzzle' in our fight against antibiotic resistance.
Topics: Humans; Anti-Bacterial Agents; Ecosystem; Bacteria; Drug Resistance, Microbial; Agriculture
PubMed: 38465465
DOI: 10.1111/1751-7915.14430 -
The Patient Mar 2024The health of a community depends on the health of its individuals; therefore, individual health behaviour can implicitly affect the health of the entire community. This...
INTRODUCTION
The health of a community depends on the health of its individuals; therefore, individual health behaviour can implicitly affect the health of the entire community. This is particularly evident in the case of infectious diseases. Because the level of prosociality in a community might determine the effectiveness of health programmes, prosocial behaviour may be a crucial disease-control resource. This study aimed to extend the literature on prosociality and investigate the role of altruism in antibiotic decision making.
METHODS
A discrete choice experiment was conducted to assess the influence of altruism on the general public's preferences regarding antibiotic treatment options. The survey was completed by 378 Swedes. Latent class analysis models were used to estimate antibiotic treatment characteristics and preference heterogeneity. A three-class model resulted in the best model fit, and altruism significantly impacted preference heterogeneity.
RESULTS
Our findings suggest that people with higher altruism levels had more pronounced preferences for treatment options with lower contributions to antibiotic resistance and a lower likelihood of treatment failure. Furthermore, altruism was statistically significantly associated with sex, education, and health literacy.
CONCLUSIONS
Antibiotic awareness, trust in healthcare systems, and non-discriminatory priority setting appear to be structural elements conducive to judicious and prosocial antibiotic behaviour. This study suggests that prosocial messages could help to decrease the demand for antibiotic treatments.
Topics: Humans; Altruism; Sweden; Drug Resistance, Microbial; Anti-Bacterial Agents; Scandinavians and Nordic People
PubMed: 38117400
DOI: 10.1007/s40271-023-00666-3 -
Pathogens and Disease Feb 2024Antibiotic resistance (ATBR) is increasing every year as the overuse of antibiotics (ATBs) and the lack of newly emerging antimicrobial agents lead to an efficient... (Review)
Review
Antibiotic resistance (ATBR) is increasing every year as the overuse of antibiotics (ATBs) and the lack of newly emerging antimicrobial agents lead to an efficient pathogen escape from ATBs action. This trend is alarming and the World Health Organization warned in 2021 that ATBR could become the leading cause of death worldwide by 2050. The development of novel ATBs is not fast enough considering the situation, and alternative strategies are therefore urgently required. One such alternative may be the use of non-thermal plasma (NTP), a well-established antimicrobial agent actively used in a growing number of medical fields. Despite its efficiency, NTP alone is not always sufficient to completely eliminate pathogens. However, NTP combined with ATBs is more potent and evidence has been emerging over the last few years proving this is a robust and highly effective strategy to fight resistant pathogens. This minireview summarizes experimental research addressing the potential of the NTP-ATBs combination, particularly for inhibiting planktonic and biofilm growth and treating infections in mouse models caused by methicillin-resistant Staphylococcus aureus or Pseudomonas aeruginosa. The published studies highlight this combination as a promising solution to emerging ATBR, and further research is therefore highly desirable.
Topics: Anti-Bacterial Agents; Plasma Gases; Animals; Humans; Biofilms; Pseudomonas aeruginosa; Mice; Methicillin-Resistant Staphylococcus aureus; Drug Resistance, Bacterial; Drug Resistance, Microbial; Pseudomonas Infections; Disease Models, Animal; Staphylococcal Infections
PubMed: 38730561
DOI: 10.1093/femspd/ftae007 -
MicrobiologyOpen Aug 2023Antibiotic resistance is a major global health threat. Agricultural use of antibiotics is considered to be a main contributor to the issue, influencing both animals and...
Antibiotic resistance is a major global health threat. Agricultural use of antibiotics is considered to be a main contributor to the issue, influencing both animals and humans as defined by the One Health approach. The purpose of the present study was to determine the abundance of antibiotic-resistant bacterial populations and the overall bacterial diversity of cattle farm soils that have been treated with animal manure compost. Soil and manure samples were collected from different sites at Tullimba farm, NSW. Cultures were grown from these samples in the presence of 11 commonly used antibiotics and antibiotic-resistant bacteria (ARB) colonies were identified. Soil and manure bacterial diversity was also determined using 16S ribosomal RNA next-generation sequencing. Results showed that ARB abundance was greatest in fresh manure and significantly lower in composted manure. However, the application of composted manure on paddock soil led to a significant increase in soil ARB abundance. Of the antibiotics tested, the number of ARB in each sample was greatest for antibiotics that inhibited the bacterial cell wall and protein synthesis. Collectively, these results suggest that the transfer of antibiotic resistance from composted animal manure to soil may not be solely mediated through the application of live bacteria and highlight the need for further research into the mechanism of antibiotic resistance transfer.
Topics: Humans; Cattle; Animals; Soil; Livestock; Angiotensin Receptor Antagonists; Composting; Manure; Angiotensin-Converting Enzyme Inhibitors; Agriculture; Drug Resistance, Microbial; Anti-Bacterial Agents
PubMed: 37642484
DOI: 10.1002/mbo3.1375 -
Gut Microbes 2024In small series, third-party fecal microbiota transplantation (FMT) has been successful in decolonizing the gut from clinically relevant antibiotic resistance genes... (Randomized Controlled Trial)
Randomized Controlled Trial
In small series, third-party fecal microbiota transplantation (FMT) has been successful in decolonizing the gut from clinically relevant antibiotic resistance genes (ARGs). Less is known about the short- and long-term effects of FMT on larger panels of ARGs. We analyzed 226 pre- and post-treatment stool samples from a randomized placebo-controlled trial of FMT in 100 patients undergoing allogeneic hematopoietic cell transplantation or receiving anti-leukemia induction chemotherapy for 47 ARGs. These patients have heavy antibiotic exposure and a high incidence of colonization with multidrug-resistant organisms. Samples from each patient spanned a period of up to 9 months, allowing us to describe both short- and long-term effects of FMT on ARGs, while the randomized design allowed us to distinguish between spontaneous changes vs. FMT effect. We find an overall bimodal pattern. In the first phase (days to weeks after FMT), low-level transfer of ARGs largely associated with commensal healthy donor microbiota occurs. This phase is followed by long-term resistance to new ARGs as stable communities with colonization resistance are formed after FMT. The clinical implications of these findings are likely context-dependent and require further research. In the setting of cancer and intensive therapy, long-term ARG decolonization could translate into fewer downstream infections.
Topics: Humans; Fecal Microbiota Transplantation; Anti-Bacterial Agents; Gastrointestinal Microbiome; Treatment Outcome; Drug Resistance, Microbial; Feces
PubMed: 38478462
DOI: 10.1080/19490976.2024.2327442