Sugar-based cysteine thiols recruited for oxidative stress defense and redox regulation

Low molecular weight (LMW) thiols are major contributors to cellular redox signaling. Here, we present the bacterial sugar-based LMW thiols mycothiol and bacillithiol, their role in redox regulation, and how they contribute to the maintenance of cellular redox homoeostasis and survival during conditions of oxidative stress encountered in the environment, or in the host during infections. At their relatively high cellular concentrations, mycothiol and bacillithiol primarily act as detoxifying cofactors. They contribute to multiple protecting and catalytic pathways via thiol-disulfide exchange mechanisms, including the posttranslational modification of proteins. Central to protein thiol deprotection are the kinetic cycles driven by mycoredoxin-1 and the bacilliredoxins. These enzymes have also been exploited to sense real-time changes in the cellular levels of mycothiol and bacillithiol as part of fluorescent biosensors. Future research is expected to elucidate the biological consequences of protein modifications by mycothiol and bacillithiol, particularly on redox and metabolic signaling.