AUTHOR=Bhawini Ajita , Pandey Parul , Dubey Ashutosh Prakash , Zehra Aafreen , Nath Gopal , Mishra Mukti Nath 

TITLE=RelQ Mediates the Expression of β-Lactam Resistance in Methicillin-Resistant Staphylococcus aureus

JOURNAL=Frontiers in Microbiology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2019.00339

DOI=10.3389/fmicb.2019.00339

ISSN=1664-302X

ABSTRACT=<p>An induced stringent response, which is established by an increased level of (p)ppGpp, is required for the expression of β-lactam resistance in methicillin-resistant <italic>Staphylococcus aureus</italic> (MRSA). However, it is not clear whether RSH (enzyme mediating stringent response to amino acid starvation) or small alarmone synthetases (SASs) are involved in the maintenance of (p)ppGpp level in response to β-lactams. Since the <italic>S. aureus</italic> genome encodes two active SASs (RelP and RelQ), their contribution to the expression of β-lactam resistance in MRSA was investigated. It was determined that <italic>relQ</italic> deletion renders community-associated MRSA (CA-MRSA) sensitive to β-lactams by negatively affecting the expression of <italic>mecA</italic>, and induction of (p)ppGpp synthesis by mupirocin bypasses the requirement of <italic>relQ</italic> for the expression of high-level β-lactam resistance. Surprisingly, <italic>relP</italic> deletion increased the level of β-lactam resistance. Such contradictory observations could be attributed to the fact that <italic>relQ</italic> promoter is ~5-fold stronger than the <italic>relP</italic> and is induced by oxacillin as well as deletion of either of the SASs, while <italic>relP</italic> promoter responds only to oxacillin. The stronger promoter activity of <italic>relQ</italic>, coupled with the inducibility of the <italic>relQ</italic> promoter in response to the lack of <italic>relP</italic>, results in efficient expression of <italic>relQ</italic> in the <italic>relP</italic>-deleted background. This positively affects <italic>mecA</italic> expression and renders the Δ<italic>relP</italic> strain highly resistant. These findings indicate an important role for RelQ in the expression of high-level β-lactam resistance in MRSA.</p>