Possible role of L-form switching in recurrent urinary tract infection

Mickiewicz, Katarzyna; Kawai, Yoshikazu; Drage, Lauren; Gomes, Margarida C.; Davison, Frances; Pickard, Robert; Hall, Judith G.; Mostowy, Serge; Aldridge, Phillip D.; Errington, Jeff

doi:10.1038/s41467-019-12359-3

Cited by 84 publications

(117 citation statements)

References 28 publications

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“…Noteworthy, formation of spheroplasts upon G-penicillin treatment has been reported in R. prowazekii (Wisseman et al, 1982), which can be sustained in the organism for a long time and can cause relapse of the infection (Raoult and Roux, 1999;Weissmann, 2005;Sekeyová et al, 2019). The recurrent diseases are generally believed to be caused not by reinfection, but by populations of persister cells, i.e., quiescent forms of bacteria (Fauvart et al, 2011;Brauner et al, 2016;Van den Bergh et al, 2016;Levin-Reisman et al, 2017;Trastoy et al, 2018;Mickiewicz et al, 2019). Most often persisters are represented by cell wall deficient forms (sometimes referred to as L-forms), which are believed to cause relapse of the disease long time after the patients' recovery due to antibiotic administration (Onwuamaegbu et al, 2005;Mickiewicz et al, 2019).…”

Section: Formation Of Persister Cells Upon Treatment With Ampicillin mentioning

confidence: 99%

A Robust Symbiotic Relationship Between the Ciliate Paramecium multimicronucleatum and the Bacterium Ca. Trichorickettsia Mobilis

Mironov

Sabaneyeva

2020

Front. Microbiol.

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Close reciprocal interactions in symbiotic systems have suggested the holobiont concept, in which the host and its microbiota are considered as a single entity. Ciliates are known for their ability to form symbiotic associations with prokaryotes. Relationships between the partners in such systems vary from mutualism to parasitism and differ significantly in their robustness. We assessed the viability of the ciliate Paramecium multimicronucleatum and its ability to maintain its intranuclear endosymbiont Ca. Trichorickettsia mobilis (Rickettsiaceae) after treatment with antibiotics characterized by different mode of action, such as ampicillin, streptomycin, chloramphenicol, tetracycline. The presence of endosymbionts in the host cell was determined by means of living cell observations made using differential interference contrast or fluorescence in situ hybridization with the species-specific oligonucleotide probe (FISH). Administration of antibiotics traditionally used in treatments of rickettsioses, tetracycline and chloramphenicol, depending on the concentration used and the ciliate strain treated, either caused death of both, infected and control cells, or did not affect the ability of the host to maintain the intranuclear endosymbiont. The surviving cells always manifested motile bacteria in the macronucleus. Streptomycin treatment never led to the loss of endosymbionts in any of the four infected strains, and nearly all ciliates remained viable. Ampicillin treatment never caused host cell death, but resulted in formation of filamentous and immobile oval bacterial forms. Under repeated ampicillin treatments, a part of endosymbionts was registered in the host cytoplasm, as evidenced both by FISH and transmission electron microscopy. Endosymbionts located in the host cytoplasm were enclosed in vacuoles, apparently, corresponding to autophagosomes. Nevertheless, the bacteria seemed to persist in this compartment and might cause relapse of the infection. Although the antibiotic sensitivity profile of Trichorickettsia seems to resemble that of other representatives of Rickettsiaceae, causative agents of severe diseases in humans, neither of the antibiotic treatments used in this study resulted in an aposymbiotic cell line, apparently, due to the protists’ sensitivity to tetracyclines, the drugs of preference in rickettsiosis treatment. The observed robustness of this symbiotic system makes it a good model for further elaboration of the holobiont concept.

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Section: Formation Of Persister Cells Upon Treatment With Ampicillin mentioning

confidence: 99%

A Robust Symbiotic Relationship Between the Ciliate Paramecium multimicronucleatum and the Bacterium Ca. Trichorickettsia Mobilis

Mironov

Sabaneyeva

2020

Front. Microbiol.

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“…Pleomorphism and persistence have often been cited as intertwined features in other bacteria, including pathogenic E. coli and Treponema pallidum [313,346]. A recent study provided strong evidence for the role of pleomorphism in urinary tract infection E. coli, in which cell wall-deficient L-forms were reported to confer greater tolerance to penicillin [346]. However, for Lyme Borrelia, the relationship between pleomorphism and antibiotic susceptibility is less established.…”

Section: Pleomorphymentioning

confidence: 99%

Lyme Disease Frontiers: Reconciling Borrelia Biology and Clinical Conundrums

Bamm

Mainprize

et al. 2019

Pathogens

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Lyme disease is a complex tick-borne zoonosis that poses an escalating public health threat in several parts of the world, despite sophisticated healthcare infrastructure and decades of effort to address the problem. Concepts like the true burden of the illness, from incidence rates to longstanding consequences of infection, and optimal case management, also remain shrouded in controversy. At the heart of this multidisciplinary issue are the causative spirochetal pathogens belonging to the Borrelia Lyme complex. Their unusual physiology and versatile lifestyle have challenged microbiologists, and may also hold the key to unlocking mysteries of the disease. The goal of this review is therefore to integrate established and emerging concepts of Borrelia biology and pathogenesis, and position them in the broader context of biomedical research and clinical practice. We begin by considering the conventions around diagnosing and characterizing Lyme disease that have served as a conceptual framework for the discipline. We then explore virulence from the perspective of both host (genetic and environmental predispositions) and pathogen (serotypes, dissemination, and immune modulation), as well as considering antimicrobial strategies (lab methodology, resistance, persistence, and clinical application), and borrelial adaptations of hypothesized medical significance (phenotypic plasticity or pleomorphy).

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“…It has been recently demonstrated that UPEC isolates from elderly patients with rUTI were cell-wall deficient (l-form) bacteria. This feature makes bacteria resistant to cell wall-targeting antibiotics, likely contributing to the recurrence of the infection [19]. Moreover, the increase in antibiotic resistance found in clinical UPEC isolates has made UTI management progressively costlier and more challenging [5,10,18].…”

Section: Introductionmentioning

confidence: 99%

d-Mannose Treatment neither Affects Uropathogenic Escherichia coli Properties nor Induces Stable FimH Modifications

et al. 2020

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Urinary tract infections (UTIs) are mainly caused by uropathogenic Escherichia coli (UPEC). Acute and recurrent UTIs are commonly treated with antibiotics, the efficacy of which is limited by the emergence of antibiotic resistant strains. The natural sugar d-mannose is considered as an alternative to antibiotics due to its ability to mask the bacterial adhesin FimH, thereby preventing its binding to urothelial cells. Despite its extensive use, the possibility that d-mannose exerts “antibiotic-like” activity by altering bacterial growth and metabolism or selecting FimH variants has not been investigated yet. To this aim, main bacterial features of the prototype UPEC strain CFT073 treated with d-mannose were analyzed by standard microbiological methods. FimH functionality was analyzed by yeast agglutination and human bladder cell adhesion assays. Our results indicate that high d-mannose concentrations have no effect on bacterial growth and do not interfere with the activity of different antibiotics. d-mannose ranked as the least preferred carbon source to support bacterial metabolism and growth, in comparison with d-glucose, d-fructose, and l-arabinose. Since small glucose amounts are physiologically detectable in urine, we can conclude that the presence of d-mannose is irrelevant for bacterial metabolism. Moreover, d-mannose removal after long-term exposure did not alter FimH’s capacity to bind to mannosylated proteins. Overall, our data indicate that d-mannose is a good alternative in the prevention and treatment of UPEC-related UTIs.

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Possible role of L-form switching in recurrent urinary tract infection

Cited by 84 publications

References 28 publications

A Robust Symbiotic Relationship Between the Ciliate Paramecium multimicronucleatum and the Bacterium Ca. Trichorickettsia Mobilis

A Robust Symbiotic Relationship Between the Ciliate Paramecium multimicronucleatum and the Bacterium Ca. Trichorickettsia Mobilis

Lyme Disease Frontiers: Reconciling Borrelia Biology and Clinical Conundrums

d-Mannose Treatment neither Affects Uropathogenic Escherichia coli Properties nor Induces Stable FimH Modifications

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