Dataset Information

Small Alarmone Synthetases RelP and RelQ of Staphylococcus aureus Are Involved in Biofilm Formation and Maintenance Under Cell Wall Stress Conditions.

ABSTRACT: The stringent response is characterized by the synthesis of the alarmone (p)ppGpp. The phenotypic consequences resulting from (p)ppGpp accumulation vary among species, and for several pathogenic bacteria, it has been shown that the activation of the stringent response strongly affects biofilm formation and maintenance. In Staphylococcus aureus, (p)ppGpp can be synthesized by the RelA/SpoT homolog Rel upon amino acid deprivation or by the two small alarmone synthetases RelP and RelQ under cell wall stress. We found that relP and relQ increase biofilm formation under cell wall stress conditions induced by a subinhibitory vancomycin concentration. However, the effect of (p)ppGpp on biofilm formation is independent of the regulators CodY and Agr. Biofilms formed by the strain HG001 or its (p)ppGpp-defective mutants are mainly composed of extracellular DNA and proteins. Furthermore, the induction of the RelPQ-mediated stringent response contributes to biofilm-related antibiotic tolerance. The proposed (p)ppGpp-inhibiting peptide DJK-5 shows bactericidal and biofilm-inhibitory activity. However, a non-(p)ppGpp-producing strain is even more vulnerable to DJK-5. This strongly argues against the assumption that DJK-5 acts via (p)ppGpp inhibition. In summary, RelP and RelQ play a major role in biofilm formation and maintenance under cell wall stress conditions.

SUBMITTER: Salzer A

PROVIDER: S-EPMC7533549 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Small Alarmone Synthetases RelP and RelQ of <i>Staphylococcus aureus</i> Are Involved in Biofilm Formation and Maintenance Under Cell Wall Stress Conditions.

Salzer Andrea A Keinhörster Daniela D Kästle Christina C Kästle Benjamin B Wolz Christiane C

Frontiers in microbiology 20200918

The stringent response is characterized by the synthesis of the alarmone (p)ppGpp. The phenotypic consequences resulting from (p)ppGpp accumulation vary among species, and for several pathogenic bacteria, it has been shown that the activation of the stringent response strongly affects biofilm formation and maintenance. In <i>Staphylococcus aureus</i>, (p)ppGpp can be synthesized by the RelA/SpoT homolog Rel upon amino acid deprivation or by the two small alarmone synthetases RelP and RelQ under ...[more]

PMID: 33072039

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Project description:During the stringent response, bacteria synthesize guanosine-3',5'-bis(diphosphate) (ppGpp) and guanosine-5'-triphosphate 3'-diphosphate (pppGpp), which act as secondary messengers to promote cellular survival and adaptation. (p)ppGpp 'alarmones' are synthesized and/or hydrolyzed by proteins belonging to the RelA/SpoT Homologue (RSH) family. Many bacteria also encode 'small alarmone synthetase' (SAS) proteins (e.g. RelP, RelQ) which may also be capable of synthesizing a third alarmone: guanosine-5'-phosphate 3'-diphosphate (pGpp). Here, we report the biochemical properties of the Rel (RSH), RelP and RelQ proteins from Staphylococcus aureus (Sa-Rel, Sa-RelP, Sa-RelQ, respectively). Sa-Rel synthesized pppGpp more efficiently than ppGpp, but lacked the ability to produce pGpp. Sa-Rel efficiently hydrolyzed all three alarmones in a Mn(II) ion-dependent manner. The removal of the C-terminal regulatory domain of Sa-Rel increased its rate of (p)ppGpp synthesis ca. 10-fold, but had negligible effects on its rate of (pp)pGpp hydrolysis. Sa-RelP and Sa-RelQ efficiently synthesized pGpp in addition to pppGpp and ppGpp. The alarmone-synthesizing abilities of Sa-RelQ, but not Sa-RelP, were allosterically-stimulated by the addition of pppGpp, ppGpp or pGpp. The respective (pp)pGpp-synthesizing activities of Sa-RelP/Sa-RelQ were compared and contrasted with SAS homologues from Enterococcus faecalis (Ef-RelQ) and Streptococcus mutans (Sm-RelQ, Sm-RelP). Results indicated that EF-RelQ, Sm-RelQ and Sa-RelQ were functionally equivalent; but exhibited considerable variations in their respective biochemical properties, and the degrees to which alarmones and single-stranded RNA molecules allosterically modulated their respective alarmone-synthesizing activities. The respective (pp)pGpp-synthesizing capabilities of Sa-RelP and Sm-RelP proteins were inhibited by pGpp, ppGpp and pppGpp. Our results support the premise that RelP and RelQ proteins may synthesize pGpp in addition to (p)ppGpp within S. aureus and other Gram-positive bacterial species.

Dataset Information

Small Alarmone Synthetases RelP and RelQ of Staphylococcus aureus Are Involved in Biofilm Formation and Maintenance Under Cell Wall Stress Conditions.

Publications

Small Alarmone Synthetases RelP and RelQ of <i>Staphylococcus aureus</i> Are Involved in Biofilm Formation and Maintenance Under Cell Wall Stress Conditions.

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