Acinetobacter baumannii defends against oxidative stress through a Mn2+-dependent small RNA-mediated suppression of type VI secretion system

Abstract

Type VI secretion system (T6SS) is utilized by many Gram negative bacteria for eliminating competing bacterial species and manipulating host cells. Acinetobacter baumannii ATCC 17978 utilizes T6SS at the expense of losing pAB3 plasmid to induce contact-dependent killing of competitor microbes, resulting in the loss of antibiotic resistance carried by pAB3. However, the regulatory network associated with T6SS in A. baumannii remains poorly understood. Here, we identified an Mn2+-dependent post-transcriptional regulation of T6SS mediated by a bonafide small RNA, AbsR28. A. baumannii utilizes MumT (Mn2+-uptake inner membrane transporter) for the uptake of extracellular Mn2+ during oxidative stress. We demonstrate that the abundance of intracellular Mn2+ enables complementary base-pairing of AbsR28-tssM mRNA (that translated to TssM, one of the vital inner membrane components of T6SS), inducing RNase E-mediated degradation of tssM mRNA and resulting in T6SS repression. Thus, AbsR28 mediates a crosstalk between MumT and T6SS in A. baumannii. IMPORTANCESmall RNAs (sRNAs) are identified as critical components within the bacterial regulatory networks involved in fine regulation of virulence-associated factors. The sRNA-mediated regulation of Acinetobacter baumanniis T6SS was unchartered. Our findings reveal a novel underlying mechanism of an Mn2+-dependent sRNA-mediated regulation of T6SS in A. baumannii. We show that binding of Mn2+ to AbsR28 aids in the complementary base-pairing of AbsR28-tssM mRNA, resulting in RNase E-mediated processing of tssM and T6SS repression. The findings also shed light on A. baumanniis preference for antibiotic resistance over contact-dependent killing during infection.