Extracellular Beta-lactamase Secretion in Heteroresistant Bacteria Confer Resistance Against Piperacillin-Tazobactam Restricted; Files Only

Abstract

Heteroresistance (HR) is a form of resistance where a phenotypically unstable minority resistance subpopulation coexists with a susceptible population; it is an emerging public health threat in that it further complicates antibiotic resistance. The mechanism of HR is an area of ongoing study. This study investigates the role of beta-lactamase secretion in conferring antibiotic resistance against piperacillin-tazobactam in heteroresistant bacteria. We observed extracellular secretion of beta-lactamase in HR isolates rescues nearby susceptible populations and enable it to survive at otherwise lethal antibiotic concentrations. The presence of secreted beta-lactamase in media causes an increase in minimum inhibitory concentrations (MIC) against bacterial isolates and the increase in MIC can exceed clinical breakpoint concentration for antibiotics. We also observed detoxification of agar plates by HR isolates secreting beta-lactamase. This work demonstrates the role of extracellular beta-lactamase secretion in enabling the growth of susceptible strains under antibiotic exposure and elucidate another mechanism for heteroresistance.

Table of Contents

Introduction .................................................................................................................................................. 1

Results ........................................................................................................................................................... 4

Discussions .................................................................................................................................................. 10

Methods ...................................................................................................................................................... 11

Supplementary Information ....................................................................................................................... 14

References .................................................................................................................................................. 16

About this Honors Thesis

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School	Emory College
Department	Biology
Degree	B.A.
Submission	Honors Thesis
Language	English
Research Field	Biology, Microbiology
Keyword	Extracellular Secretion Beta-lactamase Piperacillin Tazobactam Heteroresistance Antibiotic Resistance
Committee Chair / Thesis Advisor	Weiss, David, Emory University
Committee Members	Corbett, Anita, Emory University Kim, Minsu, Emory University

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