In Pseudomonas aeruginosa as well as in several Pseudomonas spp., the two-component system (TCS) CbrA/CbrB controls a variety of metabolic and behavioral traits needed for adaptation to changing environmental conditions. The histidine kinase CbrA and the response regulator CbrB constitute a TCS that, together with the Crc system, controls carbon metabolic flow in Pseudomonas species, allowing the utilization of preferred carbon sources and establishing a carbon/nitrogen balance. In P.

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... , CbrB activates the transcription of the CrcZ RNA. CrcZ is a regulatory RNA involved in carbon catabolite repression (CCR) and acts as a decoy for the Hfq RNA chaperone, and thus antagonizes the function of Hfq/Crc repressive complexes on catabolic genes. The CbrA/CbrB system has several functions besides the control of catabolic pathways. It is also involved in the regulation of swarming, biofilm formation, cytotoxicity and antibiotic resistance. In this study, the effect of CbrB on crcZ gene expression was assessed by Northern-blot analyses using a cbrB deletion mutant. In addition, the regulation of crcZ expression during anaerobiosis was studied using transcriptional reporter fusions. In addition, the possibility of harnessing CrcZ synthesis to increase antibiotic susceptibility of P. aeruginosa early stage biofilms was assessed. Two antibiotics, ciprofloxacin (CIP) cefepime (CEF), were tested in SCFManox medium in combination with preferred (succinate) and non-preferred (mannitol or lactamide) carbon sources. Our results verified the predicted CbrB, IHF, Anr, and σN consensus binding sites present in the crcZ promoter and showed that the corresponding transcription factors are necessary for transcriptional activation of CrcZ during anaerobiosis. Sub-inhibitory concentrations of CIP and CEF, when combined with lactamide, reduced biofilm formation under anoxic conditions. The minimal biofilm eradication concentration (MBEC) for CIP in SCFManox medium without addition of any C-source was 4 µg/ml; while the MBEC for CEF [...]