Marina Santiago

• Harvard University

Staphylococcus aureus is an opportunistic pathogen capable of causing many different human diseases. During colonization and infection, S. aureus will 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 that S. aureus uses to det...

Staphylococcus aureus is an opportunistic pathogen capable of causing many different human diseases. During colonization and infection, S. aureus will 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 that S. aureus uses to det...

Staphylococcus aureus is an opportunistic pathogen that can cause soft tissue infections but is also a frequent cause of foodborne illnesses. One contributing factor for this food association is its high salt tolerance allowing this organism to survive commonly used food preservation methods. How this resistance is mediated is poorly understood, pa...

Identifying targets of antibacterial compounds remains a challenging step in the development of antibiotics. We have developed a two-pronged functional genomics approach to predict mechanism of action that uses mutant fitness data from antibiotic-treated transposon libraries containing both upregulation and inactivation mutants. We treated a Staphy...

Importance: Bacterial resistance to every major class of antibiotics has emerged, and we are entering a "post-antibiotic era" where relatively minor infections can lead to serious complications or even death. The utility of an antibiotic for a specific pathogen is limited by both intrinsic and acquired factors. Identifying the repertoire of intrin...

Inactivation of the oxidative phosphorylation pathway confers resistance to gentamicin. (A) Schematic of the oxidative phosphorylation pathway is depicted here. Numbers of reads due to transposon insertions were greatly increased under conditions of exposure to gentamicin for the 11 genes illustrated. Inactivation of the oxidative phosphorylation p...

SAOUHSC_01025::Tn and SAOUHSC_01050::Tn are particularly sensitive to antibiotics that damage the cell envelope. (A) Data representative of results of analysis of the targeted pathways of the additional antibiotics tested against SAOUHSC_01025::Tn and SAOUHSC_01050::Tn mutants are shown. The abbreviations used here are as follows: mup, mupirocin; l...

A total of 80 unique genes were identified as important for fitness by treatment of pooled transposon libraries with six antibiotics. The top 20 genes with the greatest fold change in numbers of mapped reads are shown for each antibiotic. Fold change in the number of mapped reads is indicated by colored rectangles. Orange rectangles indicate genes...

Staphylococcus aureus readily develops resistance to antibiotics and achieving effective therapies to overcome resistance requires in-depth understanding of S. aureus biology. High throughput, parallel-sequencing methods for analyzing transposon mutant libraries have the potential to revolutionize studies of S. aureus, but the genetic tools to take...

The majority of bacterial proteins are dispensable for growth in the laboratory but nevertheless have important physiological roles. There are no systematic approaches to identify cell-permeable small-molecule inhibitors of these proteins. We demonstrate a strategy to identify such inhibitors that exploits synthetic lethal relationships both for sm...