Mechanisms and applications of anti-phage defenses in staphylococci

Staphylococci are skin-dwelling bacteria that cause antibiotic-resistant nosocomial infections. Bacteriophages (or phages for short) are the viral predators of bacteria and can infect and destroy their hosts within minutes of infection. This extraordinary property makes phages promising alternatives to conventional antibiotics for the treatment of drug-resistant infections. However, the successful implementation of phage therapy is confronted by several challenges. First, phages carry an inherent risk of undesirable side effects because their genomes encode many genes with unknown functions, and their molecular interactions with the bacterial hosts are poorly understood. Secondly, bacteria harbor a variety of anti-phage immune systems which threaten to undermine the effectiveness of whole-phage therapies. Therefore, gaining a better understanding of staphylococcal phages and their molecular interactions with the bacterial host is extremely important in order to develop safe and effective phage-based antimicrobials. The research described herein addresses these challenges. We have developed strategies to genetically engineer staphylococcal phages using the adaptive immune system known as CRISPR-Cas. We also discovered a novel anti-phage defense system mediated by a single multifunctional enzyme with nuclease and helicase functions. This enzyme provides robust immunity against diverse families of staphylococcal phages by targeting their nucleic acids. Knowledge gained from our findings is expected to enable the engineering of safe and effective phage-based antimicrobials that eliminate staphylococcal infections.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Microbiology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2022

Author dc:creator

• Bari, S M Nayeemul

Contributors dc:contributor

• Hatoum-Aslan, Asma
• Whitaker , Rachel
• Brooke, Christopher
• Dokland, Terje

• Stphylococci
• Bacteriophage
• Phage therapy
• Anti-phage defense
• CRISPR-Cas

Statement dc:rights

• Copyright 2022 S M Nayeemul Bari

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/115593

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F115593