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Indeed, phoP deletion mutants exhibit growth defects in murine bone marrow-derived macrophages (BMDMs) as well as attenuated virulence with reduced bacterial burden in the lungs, liver, and spleen of a mouse Mtb infection model ( phoP knockout mutant of H37Rv ( phoP into the H37Ra genome increased the bacterial persistence in murine BMDMs ( phoP mutant Mtb strain showed considerable attenuation in severe combined immunodeficient mice compared to the parental and BCG strains ( phoP deletion mutant strain conferred protective anti-TB immunity in mouse and guinea pig models, indicating its potential as a live vaccine candidate ( Figure 1 Stringent Response The stringent response is a conserved global signaling system that promotes bacterial survival in various environments, such as nutrient deprivation and other stresses ( Figure 1 )

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To address these limitations, future strategies should prioritize the inclusion of genetically diverse and geographically varied populations in genomic research, supported by harmonized phenotyping protocols and comprehensive clinical data