Histidine and its uptake are essential for the growth ofStaphylococcus aureusat low pH

Abstract

AbstractStaphylococcus aureusis an opportunistic pathogen capable of causing many different human diseases. During colonization and infection,S. aureuswill encounter a range of hostile environments, including acidic conditions such as those found on the skin and within macrophages. However, little is known about the mechanisms thatS. aureususes to detect and respond to low pH. Here, we employed a transposon sequencing approach to determine on a genome-wide level the genes required or detrimental for growth at low pH. We identified 31 genes that were essential for the growth ofS. aureusat pH 4.5 and confirmed the importance of many of them through follow up experiments using mutant strains inactivated for individual genes. Most of the genes identified code for proteins with functions in cell wall assembly and maintenance. These data suggest that the cell wall has a more important role than previously appreciated in promoting bacterial survival when under acid stress. We also identified several novel processes previously not linked to the acid stress response inS. aureus. These include aerobic respiration and histidine transport, the latter by showing that one of the most important genes,SAUSA300_0846, codes for a previously uncharacterized histidine transporter. We show that anS. aureus SAUSA300_0846mutant is unable to maintain its cytosolic pH, thereby revealing an important function for histidine and its transport in buffering the intracellular pH in bacteria.Author summaryStaphylococcus aureusis an important human bacterial pathogen that can cause a range of diseases. During infection, the pathogen will encounter a hostile environment within the human host, including acidic conditions such as those found on the skin and within macrophages. The bacterium has developed sophisticated strategies to survive and grow under such harsh conditions. Here we performed a genome wide screen to identify factors that are required by this pathogen to survive under acid stress conditions and identified several novel processes including histidine uptake. Understanding the response ofS. aureusto deal with acid stress conditions will help us better manage infections.