313HOST-DEPENDENT VARIATION IN STENOTROPHOMONAS MALTOPHILIA REPLICATION AND VIRULENCE DYNAMICS: INSIGHTS FROM MURINE INFECTION MODELSStenotrophomonas maltophilia, a notorious multidrug-resistant bacterium, is known to cause various human diseases, including pneumonia. However, there has been ongoing debate regarding its ability to replicate within mammalian hosts. To address this question, we conducted intranasal infection experiments using adult A/J mice, a well-established model organism. Our findings revealed that S. maltophilia strain K279a, a representative isolate, indeed replicated within the lungs of infected mice shortly after inoculation, showing a ten-fold increase in colony-forming units (CFU). Specifically, the lungs of A/J mice harbored approximately 10^4 CFU, facilitating bacterial growth. Furthermore, subsequent challenges with pro-inflammatory cytokines enhanced the host's resistance to bacterial colonization. Interestingly, our study also investigated the response of other mouse strains to S. maltophilia infection. We found that DBA/2 mice were capable of supporting S. maltophilia K279a growth, although to a lesser extent compared to A/J mice. In contrast, BALB/c and C57BL/6 mice failed to stimulate bacterial growth. This suggests that the ability of S. maltophilia to proliferate in mammalian hosts varies depending on the host genotype. Furthermore, our study revealed significant differences in survival rates among various S. maltophilia strains when introduced into the lungs of A/J mice. Some strains exhibited higher infectivity than K279a, while others were less infective. Additionally, clinical isolates of S. maltophilia displayed variable levels of major virulence factors, underscoring the complexity of S. maltophilia infection dynamics. In conclusion, our study sheds light on the intricate interplay between host genotype and bacterial factors in S. maltophilia infection. These findings have implications for understanding the pathogenesis of S. maltophilia-associated diseases and may inform the development of targeted therapeutic strategiesVaisakhi@ gmail.comResearch1122021Stenotrophomonas maltophilia, Pneumonia, Multidrug resistance,Intranasal infection, Host genotypeDr. Vaisakhi K SAssociate Professor, Department of Microbiology, Katuri Medical College & Hospital, Chinakondrupadu, Guntur, India