Uropathogenic Escherichia coli Metabolite-Dependent Quiescence and Persistence May Explain Antibiotic Tolerance during Urinary Tract Infection

Leatham-Jensen, Mary; Mokszycki, Matthew E.; Rowley, David; Deering, Robert W.; Camberg, Jodi L.; Sokurenko, Evgeni V.; Tchesnokova, Veronika; Frimodt-Møller, Jakob; Krogfelt, Karen A.; Nielsen, Karen Leth; Frimodt‐Møller, Niels; Sun, Gongqin; Cohen, Paul S.

doi:10.1128/msphere.00055-15

Cited by 42 publications

(36 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some other STs identified in this study are infrequently associated with UPEC, including ST10, ST12, and ST14, (Banerjee et al, 2013a ; Nichols et al, 2016 ), and ST141 (Toval et al, 2014 ; Leatham-Jensen et al, 2016 ). ST141 has also been identified in the fecal flora of healthy individuals (Leflon-Guibout et al, 2008 ).…”

Section: Discussionmentioning

confidence: 61%

Clonal Diversity, Virulence Potential and Antimicrobial Resistance of Escherichia coli Causing Community Acquired Urinary Tract Infection in Switzerland

et al. 2017

View full text Add to dashboard Cite

Objectives: The aim of this study was to assess the clonal structure, virulence potential and antibiotic susceptibility of uropathogenic Escherichia coli (UPEC) isolates causing community acquired urinary tract infection (CAUTI) in unselected primary care patients in Switzerland.Methods: We performed multilocus sequence typing, virulence factor determination, and phenotypic and genotypic antimicrobial resistance testing on 44 non-duplicate UPEC isolates.Results: Twenty-seven different sequence types (STs) were identified. Major UPEC clones were represented by 19 (43.2%) of the isolates, including E. coli ST131, ST69 (both 13.6%), ST73 (6.8%), ST10 (4.5%), ST127, ST140, (both 2.3%). Five (11.4%) isolates belonged to ST141.Aggregate virulence factor (VF) scores were highest among isolates belonging to ST127 and ST141. Overall, 50% of the isolates were susceptible to all 12 antimicrobials tested, and all isolates remained susceptible to fosfomycin and nitrofurantoin. Resistance to sulfamethoxazole and ciprofloxacin were found in 31.8, and 15.9% of the isolates, respectively. Plasmid-mediated resistance genes were detected in ST69 and ST131 and included aac(6′)-Ib-cr (2.3% of all isolates) blaCTX−M−14 and blaCTX−M−15 (9%), and mph(A) (13.6%). None of the isolates tested positive for mcr-1 or mcr-2.Conclusions: Our results show that CAUTI in Switzerland is caused by a wide variety of UPEC STs for which fosfomycin remains a good treatment option. We suggest that ST141 is an emerging clone associated with UTI in the community, and warrants closer attention. Moreover, the high rate of E. coli harboring mph(A) from patients without a history of antimicrobial therapy or hospitalization indicates that UPEC is an important reservoir for mph(A).

show abstract

Section: Discussionmentioning

confidence: 61%

Clonal Diversity, Virulence Potential and Antimicrobial Resistance of Escherichia coli Causing Community Acquired Urinary Tract Infection in Switzerland

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Indeed, the death of the superficial epithelium is intentionally induced by certain virulent UPEC to better reach deeper tissue where intermediate BECs are located and where they form QIRs and where they can persist for extended period of time. Actually, one of the main reason for high rate recurrence of infections in the bladder and resistance to antibiotics is associated to the presence of QIRs within subepithelium (Leatham-Jensen et al, 2016 ).…”

Section: The Bladder Epithelium Shows Self-defense Mechanisms Againstmentioning

confidence: 99%

UroPathogenic Escherichia coli (UPEC) Infections: Virulence Factors, Bladder Responses, Antibiotic, and Non-antibiotic Antimicrobial Strategies

2017

View full text Add to dashboard Cite

Urinary tract infections (UTIs) are one of the most common pathological conditions in both community and hospital settings. It has been estimated that about 150 million people worldwide develop UTI each year, with high social costs in terms of hospitalizations and medical expenses. Among the common uropathogens associated to UTIs development, UroPathogenic Escherichia coli (UPEC) is the primary cause. UPEC strains possess a plethora of both structural (as fimbriae, pili, curli, flagella) and secreted (toxins, iron-acquisition systems) virulence factors that contribute to their capacity to cause disease, although the ability to adhere to host epithelial cells in the urinary tract represents the most important determinant of pathogenicity. On the opposite side, the bladder epithelium shows a multifaceted array of host defenses including the urine flow and the secretion of antimicrobial substances, which represent useful tools to counteract bacterial infections. The fascinating and intricate dynamics between these players determine a complex interaction system that needs to be revealed. This review will focus on the most relevant components of UPEC arsenal of pathogenicity together with the major host responses to infection, the current approved treatment and the emergence of resistant UPEC strains, the vaccine strategies, the natural antimicrobial compounds along with innovative anti-adhesive and prophylactic approaches to prevent UTIs.

show abstract

“…The renewed scrutiny has now crucially shown that bacterial persistence to antibiotics can lead directly to antibiotic resistance [ 9 , 10 , 11 , 12 ]. This is of great importance since bacterial persisters have been found to cause recalcitrant clinical infections [ 13 , 14 , 15 , 16 , 17 , 18 ]. Nonetheless, early work implicating membrane transport in bacterial persistence to antibiotics [ 19 ] has not attracted the same level of attention.…”

Section: Introductionmentioning

confidence: 99%

A Quantitative Survey of Bacterial Persistence in the Presence of Antibiotics: Towards Antipersister Antimicrobial Discovery

Salcedo-Sora

Kell

2020

Antibiotics

View full text Add to dashboard Cite

Background: Bacterial persistence to antibiotics relates to the phenotypic ability to survive lethal concentrations of otherwise bactericidal antibiotics. The quantitative nature of the time–kill assay, which is the sector’s standard for the study of antibiotic bacterial persistence, is an invaluable asset for global, unbiased, and cross-species analyses. Methods: We compiled the results of antibiotic persistence from antibiotic-sensitive bacteria during planktonic growth. The data were extracted from a sample of 187 publications over the last 50 years. The antibiotics used in this compilation were also compared in terms of structural similarity to fluorescent molecules known to accumulate in Escherichia coli. Results: We reviewed in detail data from 54 antibiotics and 36 bacterial species. Persistence varies widely as a function of the type of antibiotic (membrane-active antibiotics admit the fewest), the nature of the growth phase and medium (persistence is less common in exponential phase and rich media), and the Gram staining of the target organism (persistence is more common in Gram positives). Some antibiotics bear strong structural similarity to fluorophores known to be taken up by E. coli, potentially allowing competitive assays. Some antibiotics also, paradoxically, seem to allow more persisters at higher antibiotic concentrations. Conclusions: We consolidated an actionable knowledge base to support a rational development of antipersister antimicrobials. Persistence is seen as a step on the pathway to antimicrobial resistance, and we found no organisms that failed to exhibit it. Novel antibiotics need to have antipersister activity. Discovery strategies should include persister-specific approaches that could find antibiotics that preferably target the membrane structure and permeability of slow-growing cells.

show abstract

Uropathogenic Escherichia coli Metabolite-Dependent Quiescence and Persistence May Explain Antibiotic Tolerance during Urinary Tract Infection

Cited by 42 publications

References 55 publications

Clonal Diversity, Virulence Potential and Antimicrobial Resistance of Escherichia coli Causing Community Acquired Urinary Tract Infection in Switzerland

Clonal Diversity, Virulence Potential and Antimicrobial Resistance of Escherichia coli Causing Community Acquired Urinary Tract Infection in Switzerland

UroPathogenic Escherichia coli (UPEC) Infections: Virulence Factors, Bladder Responses, Antibiotic, and Non-antibiotic Antimicrobial Strategies

A Quantitative Survey of Bacterial Persistence in the Presence of Antibiotics: Towards Antipersister Antimicrobial Discovery

Contact Info

Product

Resources

About