Culture shock:Bacterial adaptation and antimicrobial resistance: from lab to host

Antibiotics are used to treat infections caused by harmful bacteria. However, bacteria can develop antimicrobial resistance (AMR) towards antibiotics. AMR is now considered a major global health crisis. The Gram-positive bacteria Streptococcus pyogenes, Streptococcus agalactiae and Staphylococcus aureus are important human pathogens and are the focus in my thesis. These bacteria were all identified as priority pathogens by the World Health Organization (WHO) and are associated with AMR deaths worldwide. Novel treatments to combat infections of these bacteria are urgently needed. Host defense proteins and peptides (HDPs) are natural antibiotics produced by all living species to kill invading pathogens. Human HDPs include cathelicidin LL-37 and human group IIA secreted phospholipase A2 (hGIIA), among others. HDPs can act together to attack pathogens more efficiently. However, the effects of HDPs already present in human circulation in combination with administered antibiotics has not been extensively researched yet. Furthermore, the conditions of the infection site can significantly impact the effectiveness of antibiotics. Bacteria can sense external signals from the environment and adapt accordingly by turning different gene sets on or off. I used transposon libraries as a tool to investigate which bacterial genes are needed to confer antimicrobial resistance towards HDPs or which genes are essential for bacterial adaptation and survival. A better understanding of interactions between HDPs, antibiotics and bacterial adaptation is needed. The focus of my thesis is to bridge the gap in bacterial adaptation and antimicrobial resistance from the lab bench to the host environment.