Mechanisms and applications of anti-phage defenses in staphylococci

Bari, S M Nayeemul

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

Description

Title

Mechanisms and applications of anti-phage defenses in staphylococci

Author(s)

Bari, S M Nayeemul

Issue Date

2022-04-22

Director of Research (if dissertation) or Advisor (if thesis)

Hatoum-Aslan, Asma

Doctoral Committee Chair(s)

Hatoum-Aslan, Asma

Committee Member(s)

• Whitaker , Rachel
• Brooke, Christopher
• Dokland, Terje

Department of Study

Microbiology

Discipline

Microbiology

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

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

Abstract

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.

Graduation Semester

2022-05

Type of Resource

Thesis

Copyright and License Information

Copyright 2022 S M Nayeemul Bari

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