Glyphosate induces the synthesis of ppGpp

Cruvinel, Gabriela Torres; Neves, Henrique; Spira, Beny

doi:10.1007/s00438-018-1499-1

Cited by 9 publications

(23 citation statements)

References 39 publications

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“…Though not perfect, the inverse correlation between ppGpp concentration and growth rate in these strains validates the central role of (p)ppGpp in governing growth rates across the E. coli species, even in strains that come from very different genetic backgrounds as is the case of the ECOR collection. It is worth mentioning that in this as well as in other studies that analyzed (p)ppGpp in exponentially growing bacteria or in response to stresses other than amino acid starvation, pppGpp was below the detection level (Varik et al, 2017;Cruvinel et al, 2019).…”

supporting

confidence: 53%

“…It is well-established that the intrinsic concentration of (p)ppGpp is inversely correlated with growth rate (Ryals et al, 1982 ; Sarubbi et al, 1988 ; Potrykus et al, 2011 ; Jin et al, 2012 ). In fact, gratuitous induction of (p)ppGpp synthesis mediated by relA overexpression causes an almost instantaneous growth arrest (Schreiber et al, 1991 ; Svitil et al, 1993 ; Cruvinel et al, 2019 ). However, the vast majority of studies that analyzed this correlation used isogenic E. coli laboratory strains harboring different relA or spoT alleles.…”

Section: Diversity Of (P)ppgpp Concentrations–impact On Growth Rate Amentioning

confidence: 99%

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Diversity in E. coli (p)ppGpp Levels and Its Consequences

Spira

Ospino

2020

Front. Microbiol.

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(p)ppGpp is at the core of global bacterial regulation as it controls growth, the most important aspect of life. It would therefore be expected that at least across a species the intrinsic (basal) levels of (p)ppGpp would be reasonably constant. On the other hand, the historical contingency driven by the selective pressures on bacterial populations vary widely resulting in broad genetic polymorphism. Given that (p)ppGpp controls the expression of many genes including those involved in the bacterial response to environmental challenges, it is not surprising that the intrinsic levels of (p)ppGpp would also vary considerably. In fact, null mutations or less severe genetic polymorphisms in genes associated with (p)ppGpp synthesis and hydrolysis are common. Such variation can be observed in laboratory strains, in natural isolates as well as in evolution experiments. High (p)ppGpp levels result in low growth rate and high tolerance to environmental stresses. Other aspects such as virulence and antimicrobial resistance are also influenced by the intrinsic levels of (p)ppGpp. A case in point is the production of Shiga toxin by certain E. coli strains which is inversely correlated to (p)ppGpp basal level. Conversely, (p)ppGpp concentration is positively correlated to increased tolerance to different antibiotics such as β-lactams, vancomycin, and others. Here we review the variations in intrinsic (p)ppGpp levels and its consequences across the E. coli species.

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supporting

confidence: 53%

Section: Diversity Of (P)ppgpp Concentrations–impact On Growth Rate Amentioning

confidence: 99%

Diversity in E. coli (p)ppGpp Levels and Its Consequences

Spira

Ospino

2020

Front. Microbiol.

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“…It should be noted that addition of aromatic amino acids abolishes the stringent response induced by glyphosate treatment [37]. Lastly, the effect of glyphosate on cell growth and physiology is entirely dependent on relA [37].…”

Section: Discussionmentioning

confidence: 99%

“…We thus asked whether (p)ppGpp might be involved in the process of glyphosate-induced tolerance or persistence against ampicillin, ciprofloxacin and kanamycin. To test this possibility, time-kill curves were performed in the ΔrelA mutant, that does not accumulate (p)ppGpp in response to glyphosate [37].…”

Section: Glyphosate Effect On Tolerance and Persistence Is Independen...mentioning

confidence: 99%

Glyphosate affects persistence and tolerance but not antibiotic resistance

Ospino

Spira

2022

Preprint

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Glyphosate is a herbicide widely used in food production that blocks the synthesis of aromatic amino acids in plants and in microorganisms and also induces the accumulation of the alarmone (p)ppGpp. Resistance, tolerance and persistence to antibiotics are common phenomena that contribute to antibiotic treatment failure. There are several mechanisms through which bacteria attain tolerance or persistence to antibiotics, but all of them involve partial or complete growth inhibition. In this study we evaluated the effect of glyphosate on the resistance, tolerance, and persistence towards the antibiotics ampicillin, ciprofloxacin and kanamycin and the possible role of (p)ppGpp in this activity. Glyphosate did not affect the minimum inhibitory concentration of these antibiotics, but enhanced bacterial tolerance and/or persistence towards them. The upshift in ciprofloxacin and kanamycin tolerance was partially dependent on the presence of relA that promotes (p)ppGpp accumulation in response to glyphosate. Conversely, the strong increase in ampicillin tolerance caused by glyphosate was independent of relA. We conclude that by inducing aromatic amino acid starvation glyphosate contributes to the temporary increase in E. coli tolerance or persistence, but does not affect antibiotic resistance.

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“…Phosphonates (P valence +3) are phosphorus-containing organic molecules in which the P atom is linked directly to C in a stable chemical bond. Though less common in nature than organic phosphates, many Pn molecules, such as the antibiotic fosfomycin and the herbicide glyphosate are of clinical and environmental importance [3, 4]. The first three genes of the phn operon - phnCDE , encode an ABC-type Pn transport system.…”

Section: Introductionmentioning

confidence: 99%

Phosphate uptake by the phosphonate transport system PhnCDE

2019

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Background Phosphate is a fundamental nutrient for all creatures. It is thus not surprising that a single bacterium carries different transport systems for this molecule, each usually operating under different environmental conditions. The phosphonate transport system of E. coli K-12 is cryptic due to an 8 bp insertion in the phnE ORF. Results Here we report that an E. coli K-12 strain carrying the triple knockout Δ pitA Δ pst Δ ugp reverted the phnE mutation when plated on complex medium containing phosphate as the main phosphorus source. It is also shown that PhnCDE takes up orthophosphate with transport kinetics compatible with that of the canonical transport system PitA and that Pi-uptake via PhnCDE is sufficient to enable bacterial growth. Ugp, a glycerol phosphate transporter, is unable to take up phosphate. Conclusions The phosphonate transport system, which is normally cryptic in E. coli laboratory strains is activated upon selection in rich medium and takes up orthophosphate in the absence of the two canonical phosphate-uptake systems. Based on these findings, the PhnCDE system can be considered a genuine phosphate transport system. Electronic supplementary material The online version of this article (10.1186/s12866-019-1445-3) contains supplementary material, which is available to authorized users.

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Glyphosate induces the synthesis of ppGpp

Cited by 9 publications

References 39 publications

Diversity in E. coli (p)ppGpp Levels and Its Consequences

Diversity in E. coli (p)ppGpp Levels and Its Consequences

Glyphosate affects persistence and tolerance but not antibiotic resistance

Phosphate uptake by the phosphonate transport system PhnCDE

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