EVALUATING ANTIMICROBIAL PEPTIDE RESISTANCE AND HOST IMMUNE RESPONSES IN STAPHYLOCOCCUS AUREUS INFECTIONS

Abstract

Understanding the adaptation of Staphylococcus aureus and host immune response during infection is an important challenge with regard to the development of Antimicrobial peptide (AMP) resistance. This study tested the correlation between antimicrobial peptide resistance, immune gene expression, bacterial persistence and host survival using experimental data from a Tenebrio molitor insect infection model. Experimentally generated data (2,100 records) consisting of bacterial-load measurements, survival observations, and quantitative polymerase chain reaction data were subjected to quantitative secondary-data analysis. Nine strains of S. aureus, including the ancestor, the AMP-sensitive and the AMP-resistant variants were investigated under both control and immune-gene knockdown conditions. Bacterial load was determined by colony-forming unit counts and host immune responses by the expression of tenecin 1, tenecin 2, tenecin 4, and prophenoloxidase genes. Results showed that higher median bacterial loads were found after AMP knockdown on Day 7 (720 versus 328 CFU/100 µL). AMP knockdown was associated with a 9.0-percentage-point increase in mortality, whereas prophenoloxidase knockdown was associated with a 14.7-percentage-point increase. Immune gene expression was reduced and there were heterogeneous strain-specific survival patterns, indicating complex interactions between bacterial resistance and host defenses. Resistance classes were not however always correlated with the severity of infections. These results highlight the need for innate immune mechanisms in controlling bacterial infection and offer clues to the host-pathogen relationship associated with resistance, paving the way for further study on bacterial antimicrobial resistance and immune regulation.