Molecular mechanisms of collateral sensitivity to the antibiotic nitrofurantoin

Roemhild, Roderich; Linkevičius, Marius; Andersson, Dan I.

doi:10.1371/journal.pbio.3000612

Cited by 73 publications

(82 citation statements)

References 42 publications

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“…It has previously been demonstrated that evolution of tolerance precedes evolution of resistance (3) and may result in cross-tolerance (26) and collateral sensitivity (27) Figure 3), consistent with the lack of tolerance response at the proteome level. Interestingly, we found colonies in tolerance assays with FOS (fosfomycin), which upon re-testing by MIC displayed an elevated level of resistance and are likely spontaneous mutants ( Supplementary Figure 4), a phenomenon frequently described for this antibiotic (29).…”

Section: Downloaded Fromsupporting

confidence: 80%

Selection for Resistance to a Glyphosate-Containing Herbicide in Salmonella enterica Does Not Result in a Sustained Activation of the Tolerance Response or Increased Cross-Tolerance and Cross-Resistance to Clinically Important Antibiotics

Pöppe

Bote

Ramesh

et al. 2020

Appl Environ Microbiol

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Evolution of bacterial tolerance to antimicrobials precedes evolution of resistance and may result in cross-tolerance, cross-resistance or collateral sensitivity to other antibiotics. Transient exposure of gut bacteria to glyphosate, the world's most widely used herbicide, has been linked to the activation of the stress response and changes in susceptibility to antibiotics. In this study, we investigated whether a chronic exposure to a glyphosate-containing herbicide (GBH) results in resistance, a constitutive activation of the tolerance and stress response and cross-tolerance or cross-resistance to antibiotics. Of the ten farm animals-derived clinical isolates of Salmonella enterica subjected to experimental evolution in increasing concentrations of GBH, three isolates showed a stable resistance with mutations associated with the glyphosate target gene aroA and no fitness costs. The global quantitative proteomics analysis demonstrated activation of the cellular tolerance and stress response during the transient exposure to GBH, but not constitutively in the resistant mutants. Resistant mutants displayed no cross-resistance or cross-tolerance to antibiotics. These results suggest that while transient exposure to GBH triggers cellular tolerance response in Salmonella enterica, this response does not become genetically fixed after selection for resistance to GBH and does not result in increased cross-tolerance or cross-resistance to clinically important antibiotics under our experimental conditions. Importance Glyphosate-based herbicides (GBH) are among the world's most popular, with traces commonly found in food, feed and the environment. Such high ubiquity means that the herbicide may come into contact with various microorganisms, on which it acts as an antimicrobial and may select for resistance and cross-resistance to clinically important antibiotics. It is therefore important to estimate whether the widespread use of pesticides may be an underappreciated source of antibiotic resistant microorganisms that may compromise efficiency of antibiotic treatments in humans and animals.

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Section: Downloaded Fromsupporting

confidence: 80%

Selection for Resistance to a Glyphosate-Containing Herbicide in Salmonella enterica Does Not Result in a Sustained Activation of the Tolerance Response or Increased Cross-Tolerance and Cross-Resistance to Clinically Important Antibiotics

Pöppe

Bote

Ramesh

et al. 2020

Appl Environ Microbiol

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“…ST131 spreads between mother-infant pairs [28] likely via an oro-faecal transmission route [29], and such colonisation of infants can last for long periods [30]. Consequently, AMR gene screening can inform on treatment strategies [31] and the effect of antibiotics on microbiomes [32].…”

Section: Introductionmentioning

confidence: 99%

Plasmids shape the diverse accessory resistomes of Escherichia coli ST131

Decano

Tran

Al-Foori

et al. 2021

Access Microbiology

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The human gut microbiome includes beneficial, commensal and pathogenic bacteria that possess antimicrobial resistance (AMR) genes and exchange these predominantly through conjugative plasmids. Escherichia coli is a significant component of the gastrointestinal microbiome and is typically non-pathogenic in this niche. In contrast, extra-intestinal pathogenic E. coli (ExPEC) including ST131 may occupy other environments like the urinary tract or bloodstream where they express genes enabling AMR and host cell adhesion like type 1 fimbriae. The extent to which commensal E. coli and uropathogenic ExPEC ST131 share AMR genes remains understudied at a genomic level, and we examined this here using a preterm infant resistome. We found that individual ST131 had small differences in AMR gene content relative to a larger shared resistome. Comparisons with a range of plasmids common in ST131 showed that AMR gene composition was driven by conjugation, recombination and mobile genetic elements. Plasmid pEK499 had extended regions in most ST131 Clade C isolates, and it had evidence of a co-evolutionary signal based on protein-level interactions with chromosomal gene products, as did pEK204 that had a type IV fimbrial pil operon. ST131 possessed extensive diversity of selective type 1, type IV, P and F17-like fimbriae genes that was highest in subclade C2. The structure and composition of AMR genes, plasmids and fimbriae vary widely in ST131 Clade C and this may mediate pathogenicity and infection outcomes.

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“…In addition, nitrofurantoin stimulates the production of reactive oxygen species (ROS) ( Garcia Martinez et al, 1995 ) that can facilitate the entry of aminoglycosides and subsequent bacterial killing ( Ezraty et al, 2013 ). Furthermore, aminoglycosides have collateral sensitivity with many antibiotics, nitrofurantoin has also been reported to be collateral sensitivity with tigecycline, mecillinam and protamine, therefore, whether nitrofurantoin has synergistic sensitivity with amikacin is also very much studied ( Suzuki et al, 2014 ; Pal et al, 2015 ; Roemhild et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Nitrofurantoin Combined With Amikacin: A Promising Alternative Strategy for Combating MDR Uropathogenic Escherichia coli

Zhong

Cui

et al. 2020

Front. Cell. Infect. Microbiol.

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Urinary tract infections (UTI) are common infections that can be mild to life threatening. However, increased bacterial resistance and poor patient compliance rates have limited the effectiveness of conventional antibiotic therapies. Here, we investigated the relationship between nitrofurantoin and amikacin against 12 clinical MDR uropathogenic Escherichia coli (UPEC) strains both in vitro and in an experimental Galleria mellonella model. In vitro synergistic effects were observed in all 12 test strains by standard checkerboard and time-kill assays. Importantly, amikacin or nitrofurantoin at half of the clinical doses were not effective in the treatment of UPEC infections in the G. mellonella model but the combination therapy significantly increased G. mellonella survival from infections caused by all 12 study UPEC strains. Taken together, these results demonstrated synergy effects between nitrofurantoin and amikacin against MDR UPEC.

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Molecular mechanisms of collateral sensitivity to the antibiotic nitrofurantoin

Cited by 73 publications

References 42 publications

Selection for Resistance to a Glyphosate-Containing Herbicide in Salmonella enterica Does Not Result in a Sustained Activation of the Tolerance Response or Increased Cross-Tolerance and Cross-Resistance to Clinically Important Antibiotics

Selection for Resistance to a Glyphosate-Containing Herbicide in Salmonella enterica Does Not Result in a Sustained Activation of the Tolerance Response or Increased Cross-Tolerance and Cross-Resistance to Clinically Important Antibiotics

Plasmids shape the diverse accessory resistomes of Escherichia coli ST131

Nitrofurantoin Combined With Amikacin: A Promising Alternative Strategy for Combating MDR Uropathogenic Escherichia coli

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