• Indian researchers have unravelled the mechanism by which hydrogen sulphide (H2S) gas produced by bacteria protects them from antibiotics and plays a key role in helping bacteria develop drug resistance. And by blocking/disabling the enzyme that triggers the biosynthesis of hydrogen sulphide in bacteria, the researchers from Bengaluru’s Indian Institute of Science (IISc) and Indian Institute of Science Education and Research (IISER) Pune, have been able to reverse antibiotic resistance in E. coli bacteria; E. coli bacteria were isolated from patients suffering from urinary tract infection.
• Antibiotics kill by increasing the levels of reactive oxygen species (oxidative stress) inside bacterial cells.
• So any mechanism that detoxifies or counters reactive oxygen species generated by antibiotics will reduce the efficacy of antibiotics.
• “Hydrogen sulphide does this to nullify the effect of antibiotics.
• When bacteria face reactive oxygen species a protective mechanism in the bacteria kicks in and more hydrogen sulphide is produced.” Hydrogen sulphide successfully counters reactive oxygen species and reduces the efficacy of antibiotics.
• Hydrogen sulphide released by the molecule was able to counter reactive oxygen species and reduce the ability of antibiotics to kill bacteria.
• Bacteria that are genetically resistant to antibiotics actually become sensitive to antibiotics when hydrogen sulphide synthesis is inhibited.
• The multidrug-resistant E. coli regained its ability to survive antibiotics when hydrogen sulphide was once again supplied by introducing the small molecule synthesised.

• The researchers identified that E. coli has two modes of respiration involving two different enzymes.
• The hydrogen sulphide gas produced shuts down E. coli’s aerobic respiration by targeting the main enzyme (cytochrome bo oxidase (CyoA)) responsible for it.
• E. coli then switches over to an alternative mode of respiration by relying on a different enzyme — cytochrome bd oxidase (Cydb).
• Besides enabling respiration, the Cydb enzyme detoxifies the reactive oxygen species produced by antibiotics and blunts the action of antibiotics.
• Hydrogen sulphide activates the Cydb enzyme, which, in turn, is responsible for increasing resistance towards antibiotics.
• If we have a drug-like molecule(s) that blocks hydrogen sulphide production and inhibits Cydb enzyme activity then the combination will be highly lethal against multidrug-resistant bacteria.
• This combination can also be used along with antibiotics to effectively treat difficult-to-cure bacterial infections.
• The link between hydrogen sulphide and Cydb enzyme in the emergence of drug resistance is another key finding of the study.

• Reactive oxygen species (ROS) are chemically reactive chemical species containing oxygen.
• Examples include peroxides, superoxide, hydroxyl radical, and singlet oxygen.
• In a biological context, ROS are formed as a natural byproduct of the normal metabolism of oxygen and have important roles in cell signaling and homeostasis.
• However, during times of environmental stress (e.g., UV or heat exposure), ROS levels can increase dramatically.
• This may result in significant damage to cell structures. Cumulatively, this is known as oxidative stress. ROS are also generated by exogenous sources such as ionizing radiation.

Source: TH & Wiki