Sub-Inhibitory concentrations of SOS-Response inducing antibiotics stimulate integrase expression and excision of pathogenicity islands in uropathogenic Escherichia coli strain 536

Chittò, Marco; Berger, Michael; Klotz, Luisa; Dobrindt, Ulrich

doi:10.1016/j.ijmm.2019.151361

Cited by 16 publications

(29 citation statements)

References 57 publications

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“…When lysogenized bacteria undergo DNA damage, bacteriophages switch to the lytic cycle, presumably to escape from an endangered host and disperse in the environment (Little, 2005). This early observation in phage biology underlies a phenomenon shared by other mobile genetic elements (MGEs), such as integrons (Guerin et al, 2009), chromosome cassettes (Liu et al, 2017), pathogenicity islands (Chittò et al, 2020) and integrative and conjugative elements (ICEs) (Beaber et al, 2004;Auchtung et al, 2005). Figure 2 depicts the relationship of the SOS response with MGEs.…”

Section: Relationship Between Sos Response and Mobile Genetic Elementsmentioning

confidence: 99%

Sending out an SOS - the bacterial DNA damage response

et al. 2022

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The term "SOS response" was first coined by Radman in 1974, in an intellectual effort to put together the data suggestive of a concerted gene expression program in cells undergoing DNA damage. A large amount of information about this cellular response has been collected over the following decades. In this review, we will focus on a few of the relevant aspects about the SOS response: its mechanism of control and the stressors which activate it, the diversity of regulated genes in different species, its role in mutagenesis and evolution including the development of antimicrobial resistance, and its relationship with mobile genetic elements.

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Section: Relationship Between Sos Response and Mobile Genetic Elementsmentioning

confidence: 99%

Sending out an SOS - the bacterial DNA damage response

et al. 2022

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“…In addition to IHF, the host protein Fis appears to be involved in the integrative process of temperate bacteriophages 36 . We therefore decided to test if these proteins are involved in the excision process of PAI I 536 -VI 536 and constructed isogenic ihfA/B and fis mutants of E. coli 536 reporter strains for the measurement of PAI I 536 -VI 536 stability 37 . We found that Fis only plays a minor stabilizing role on individual PAIs.…”

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confidence: 99%

IHF stabilizes pathogenicity island I of uropathogenic Escherichia coli strain 536 by attenuating integrase I promoter activity

Chittò

Berger

et al. 2020

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Pathogenicity islands (PAIs) represent horizontally acquired chromosomal regions and encode their cognate integrase, which mediates chromosomal integration and excision of the island. These site-specific recombination reactions have to be tightly controlled to maintain genomic stability, and their directionality depends on accessory proteins. The integration host factor (IHF) and the factor for inversion stimulation (Fis) are often involved in recombinogenic complex formation and controlling the directionality of the recombination reaction. We investigated the role of the accessory host factors IHF and Fis in controlling the stability of six PAIs in uropathogenic Escherichia coli strain 536. By comparing the loss of individual PAIs in the presence or absence of IHF or Fis, we showed that IHF specifically stabilized PAI I536 and that in particular the IHFB subunit seems to be important for this function. We employed complex genetic studies to address the role of IHF in PAI I536-encoded integrase (IntI) expression. Based on different YFP-reporter constructs and electrophoretic mobility shift assays we demonstrated that IntI acts a strong repressor of its own synthesis, and that IHF binding to the intI promoter region reduces the probability of intI promoter activation. Our results extend the current knowledge of the role of IHF in controlling directionality of site specific recombination reactions and thus PAI stability.

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“…Nitroxoline is thought to chelate divalent cations, thereby interfering with transcription by inhibiting the RNA polymerase as well as interfering with outer membrane integrity, subsequently leading to bacterial death [44,45]. Additionally, nitroxoline induces the SOS response and may, therefore, cause DNA damage similar to the structurally related quinolone antibiotics [46]. Based on the available data, there is no parallel resistance between nitroxoline and the first-line drugs recommended for UTI treatment.…”

Section: Co-localisation Of Transferable Resistance To Cotrimoxazole Esbl and Quinolonesmentioning

confidence: 99%

Compared with Cotrimoxazole Nitroxoline Seems to Be a Better Option for the Treatment and Prophylaxis of Urinary Tract Infections Caused by Multidrug-Resistant Uropathogens: An In Vitro Study

et al. 2021

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The resistance of uropathogens to various antibiotics is increasing, but nitroxoline remains active in vitro against some relevant multidrug resistant uropathogenic bacteria. E. coli strains, which are among the most common uropathogens, are unanimously susceptible. Thus, nitroxoline is an option for the therapy of urinary tract infections caused by multiresistant bacteria. Since nitroxoline is active against bacteria in biofilms, it will also be effective in patients with indwelling catheters or foreign bodies in the urinary tract. Cotrimoxazole, on the other hand, which, in principle, can also act on bacteria in biofilms, is frequently inactive against multiresistant uropathogens. Based on phenotypic resistance data from a large number of urine isolates, structural characterisation of an MDR plasmid of a recent ST131 uropathogenic E. coli isolate, and publicly available genomic data of resistant enterobacteria, we show that nitroxoline could be used instead of cotrimoxazole for intervention against MDR uropathogens. Particularly in uropathogenic E. coli, but also in other enterobacterial uropathogens, the frequent parallel resistance to different antibiotics due to the accumulation of multiple antibiotic resistance determinants on mobile genetic elements argues for greater consideration of nitroxoline in the treatment of uncomplicated urinary tract infections.

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Sub-Inhibitory concentrations of SOS-Response inducing antibiotics stimulate integrase expression and excision of pathogenicity islands in uropathogenic Escherichia coli strain 536

Cited by 16 publications

References 57 publications

Sending out an SOS - the bacterial DNA damage response

Sending out an SOS - the bacterial DNA damage response

IHF stabilizes pathogenicity island I of uropathogenic Escherichia coli strain 536 by attenuating integrase I promoter activity

Compared with Cotrimoxazole Nitroxoline Seems to Be a Better Option for the Treatment and Prophylaxis of Urinary Tract Infections Caused by Multidrug-Resistant Uropathogens: An In Vitro Study

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