Abstract
The facultative anaerobe, Bacillus cereus, causes diarrheal diseases in humans. Its ability to deal with oxygen availability is recognized to be critical for pathogenesis. The B. cereus genome comprises a gene encoding a protein with high similarities to the redox regulator, Rex, which is a central regulator of anaerobic metabolism in Bacillus subtilis and other Gram-positive bacteria. Here, we showed that B. cereus rex is monocistronic and down-regulated in the absence of oxygen. The protein encoded by rex is an authentic Rex transcriptional factor since its DNA binding activity depends on the NADH/NAD+ ratio. Rex deletion compromised the ability of B. cereus to cope with external oxidative stress under anaerobiosis while increasing B. cereus resistance against such stress under aerobiosis. The deletion of rex affects anaerobic fermentative and aerobic respiratory metabolism of B. cereus by decreasing and increasing, respectively, the carbon flux through the NADH-recycling lactate pathway. We compared both the cellular proteome and exoproteome of the wild-type and Δrex cells using a high throughput shotgun label-free quantitation approach and identified proteins that are under control of Rex-mediated regulation. Proteomics data have been deposited to the ProteomeXchange with identifier PXD000886. The data suggest that Rex regulates both the cross-talk between metabolic pathways that produce NADH and NADPH and toxinogenesis, especially in oxic conditions.
Highlights
Bacillus cereus is a Gram-positive, facultative-anaerobe, rodshaped endospore-forming human pathogen
Changes in oxygen availability can influence the relative levels of the dinucleotide, NAD+ and NADH, in the cell, and such changes are sensed by the transcriptional regulator, Rex, in B. subtilis [12] as in other Gram-positive bacteria [13,14,15,16,17,18,19]
Using real-time RT-PCR, we investigated the expression of B. cereus rex under aerobiosis and anaerobiosis in early-growing ATCC 14579 cells
Summary
Bacillus cereus is a Gram-positive, facultative-anaerobe, rodshaped endospore-forming human pathogen. The most extensively studied diarrheal enterotoxins are hemolysin BL (Hbl), nonhemolytic enterotoxin (Nhe), and cytotoxin K (CytK) [4,5]. These enterotoxins are secreted via the Sec translocation pathway [6]. To grow and produce virulence factors in the human intestine, B. cereus must adapt its metabolism, and regulates its proteome [9] in response to changes in oxygen availability. In B. cereus, ResD, Fnr and LdhA regulate both catabolism and enterotoxin production under both aerobic and anaerobic growth conditions, probably through a regulatory complex [26]. A role of Rex in toxinogenesis has not yet been reported in B. cereus or in any other organism
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