Molecular Mechanisms of Antibiotic Resistance – Part I

Baylay, Alison J.; Piddock, Laura J. V.; Webber, Mark A.

doi:10.1002/9781119593522.ch1

Cited by 9 publications

(7 citation statements)

References 169 publications

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“…These include genes involved in cellular response to antimicrobials ( ramR, smvA, arnA ), biosynthesis of cellular metabolite and components ( stiC, glf, cadC, bcsB, ccmA ), and response to cellular stress ( rpoS ). Particularly, RamR acts as a main transcriptional repressor of the MDR efflux pump acrAB-tolC complex 24 , while ArnA catalyzes the maturation of lipid A and resistance to polymyxins 25 . Notably, the remaining H antigen of the monophasic serotype ( fliC ) has the highest dN/dS estimate (= 3.31).…”

Section: Resultsmentioning

confidence: 99%

Multidrug resistance plasmids underlie clonal expansions and international spread ofSalmonella entericaserotype 4,[5],12,i:- ST34 in Southeast Asia

The

Pham

Tuyen

et al. 2023

Preprint

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Salmonella enterica serotype 4,[5],12,i:- (Typhimurium monophasic variant) of sequence type (ST) 34 has emerged as the predominant pandemic genotype in recent decades. Despite increasing reports of resistance to antimicrobials in Southeast Asia, Salmonella ST34 population structure and evolution remained understudied in the region. Here we performed detailed genomic investigations on 454 ST34 genomes collected from Vietnam and diverse geographical sources to elucidate the pathogen epidemiology, evolution and antimicrobial resistance. We showed that ST34 has been introduced into Vietnam in at least nine occasions since 2000, forming five co-circulating major clones responsible for paediatric diarrhoea and bloodstream infection. Most expansion events were associated with acquisitions of large multidrug resistance plasmids of IncHI2 or IncA/C2. Particularly, the self-conjugative IncA/C2 pST34VN2 (co-transferring blaCTX-M-55, mcr-3.1, and qnrS1) underlies local expansion and intercontinental spread in two separate ST34 clones. At the global scale, Southeast Asia was identified as a hotspot for the emergence and dissemination of multidrug resistant Salmonella ST34, and mutation analysis suggests of selection in antimicrobial responses and key virulence factors. Our work enriches the understanding on epidemiology and evolution of this variant in Southeast Asia, and determines that multidrug resistance plasmids have driven its local and potentially global success.

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Section: Resultsmentioning

confidence: 99%

Multidrug resistance plasmids underlie clonal expansions and international spread ofSalmonella entericaserotype 4,[5],12,i:- ST34 in Southeast Asia

The

Pham

Tuyen

et al. 2023

Preprint

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“…ABC pumps are different from other types of multidrug efflux pumps because they are categorized as primary transporters. This means that their transport function is directly connected to the hydrolysis of ATP, instead of relying on ion transport like other types of pumps ( Baylay et al., 2019 ; Thomas and Tampé, 2020 ).…”

Section: Efflux Pumpsmentioning

confidence: 99%

A review of the mechanisms that confer antibiotic resistance in pathotypes of E. coli

Nasrollahian,

Graham,

Halaji

2024

Front. Cell. Infect. Microbiol.

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The dissemination of antibiotic resistance in Escherichia coli poses a significant threat to public health worldwide. This review provides a comprehensive update on the diverse mechanisms employed by E. coli in developing resistance to antibiotics. We primarily focus on pathotypes of E. coli (e.g., uropathogenic E. coli) 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 β-lactamases (ESBLs) and carbapenemases in conferring resistance to β-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 E. coli, 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 E. coli 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.

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“…It has been shown that 86% of all pneumonia is considered VAP [ 7 , 14 ], which is highly worrying due to the fact the P. aeruginosa and K. pneumoniae are both common causes of VAP. Both bacteria are highly resistant [ 35 , 56 ], with K. pneumoniae being colloquially termed a “collector” of resistance, typically gaining additional resistance via horizontal gene transfer from other resistant bacteria like VRE and P. aeruginosa [ 25 , 57 ]. More worrying still is the discovery that K. pneumoniae and P. aeruginosa can form multi-species biofilms, sharing resistances and protection [ 25 ].…”

Section: Transmission Resistance and Persistencementioning

confidence: 99%

“…Due to this incidence rate, C. difficile is considered the leading cause of HAIs in the US [ 17 , 18 ]. This high rate of infection also leads to a high economic burden [ 3 ], with HAIs contributing to €1.5 billion per year in Europe and costing more than $4.8 billion in the US [ 15 , 17 , 18 , 35 ]. In addition, it has been shown that in 2016, in Europe, a prolonged length of hospital stay of up to 8 days accumulated an overall extra cost of €1,228,782 per year, which has increased with time [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Novel Detection of Nasty Bugs, Prevention Is Better than Cure

Strom

Crowley

Shigdar

2020

IJMS

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Hospital-acquired infections (HAIs) are a growing concern around the world. They contribute to increasing mortality and morbidity rates and are an economic threat. All hospital patients have the potential to contract an HAI, but those with weakened or inferior immune systems are at highest risk. Most hospital patients will contract at least one HAI, but many will contract multiple ones. Bacteria are the most common cause of HAIs and contribute to 80–90% of all HAIs, with Staphylococcus aureus, Clostridium difficile, Escherichia coli, Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae accounting for the majority. Each of these bacteria are highly resistant to antibiotics and can produce a protective film, known as a biofilm, to further prevent their eradication. It has been shown that by detecting and eradicating bacteria in the environment, infection rates can be reduced. The current methods for detecting bacteria are time consuming, non-specific, and prone to false negatives or false positives. Aptamer-based biosensors have demonstrated specific, time-efficient and simple detection, highlighting the likelihood that they could be used in a similar way to detect HAI-causing bacteria.

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Molecular Mechanisms of Antibiotic Resistance – Part I

Cited by 9 publications

References 169 publications

Multidrug resistance plasmids underlie clonal expansions and international spread ofSalmonella entericaserotype 4,[5],12,i:- ST34 in Southeast Asia

Multidrug resistance plasmids underlie clonal expansions and international spread ofSalmonella entericaserotype 4,[5],12,i:- ST34 in Southeast Asia

A review of the mechanisms that confer antibiotic resistance in pathotypes of E. coli

Novel Detection of Nasty Bugs, Prevention Is Better than Cure

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