SALMONELLA
1. Context:
- Rapid use of traditional antibiotics gave rise to the emergence of drug-resistant Salmonella serovars.
- Samonella Typhimurium ST313, a non-typhoidal variant, causes bloodstream infection in the malnourished, immunocompromised population.
- Recent studies found the emergence of multi-drug resistant (MTR) Salmonella typhimurium DT104 that causes infections in humans & cattle.
2.Protection:
- MDR phenotype by Salmonella Genomic Island-1(SGI-1), confers protection against antibiotics like ampicillin, chloramphenicol, florfenicol, streptomycin, sulphonamides, and tetracycline.
- Emergence of extensively drug-resistant(XDR) S.typhimuriu ST313, is resistant against extended-spectrum posed a threat to global health.
- Annual incidence of 360 cases of typhoid fever per 100000 people, with an annual estimate of 4.5 million cases & 8930 deaths in India.
- The continuous adaption of this bacteria to antibiotics creates a risk of developing antimicrobial resistance in future.
- This is the reason why it is essential to study the effect of new drugs & find their potential targets in Salmonella.
- The outer membrane porins of Salmonella play an important role in the survival of the bacteria in the presence of antibiotics.
- In a study, it was shown that deleting outer membrane protein A(OmpA) from Salmonella hampered its survival in the presence of 2 beta-lactam drugs-ceftazidime and meropenem.
- OmpA is one of the most abundant barrel-shaped porin proteins localised in the outer membrane of Salmonella.
3. Absence of OmpA:
- The absence of OmpA in Salmonella hampers the stability of the bacterial outer membrane & reduces the expression of flux pump genes.
- The outer membrane protein A could restrict the entry of antibiotics into bacteria, thus improving the survival of the pathogen under antibiotic treatment.
- Removing OmpA resulted in a greater intake of ceftazidime, meropenem which ultimately killed the mutant bacteria by disrupting its outer envelope.
- The disruption of OmpA can effectively reduce the anti-biotic resistant persister population of Salmonella.
- Administration of ceftazidime in mice infected with the OmpA-deleted strain of Salmonella cured the infection & proved that OmpA plays a crucial role in antimicrobial resistance.
- The loss of integrity of the bacterial outer membrane in the absence of OmpA made the bacteria highly susceptible to killing by the host's innate immune system.
- Other gram-negative pathogens use outer membrane porins for various purposes, ranging from maintaining outer membrane stability to developing antimicrobial resistance.

4.AMR Risk:
The strategy to target outer membrane protein A of Salmonella can be used to develop novel antimicrobials for other pathogens that can effectively reduce the risk of antimicrobial resistance in future.
Source: The Hindu

