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Measuring Bacterial Load and Immune Responses in Mice Infected with Listeria monocytogenes
Published on: August 9, 2011
A pbpB1 mutation causing reduced β-lactam susceptibility in clinical Listeria monocytogenes isolates
Sabrina Wamp1, Rosalyn Wagner2, Franziska Schuler3
1FG11 Division of Enteropathogenic Bacteria and Legionella, Consultant Laboratory for Listeria, Robert Koch Institute, Wernigerode, Germany.
Abstract:
Listeriosis is a severe foodborne infection and associated with high mortality. Treatment is based on ampicillin, amoxicillin or penicillin, often combined with gentamicin, but meropenem is also used occasionally. β-lactam resistant Listeria monocytogenes isolates are infrequently described but the mechanism of resistance is not known. A clinical L. monocytogenes isolate with reduced β-lactam susceptibility was collected from a German listeriosis patient. Resistance profiling, whole genome sequencing, comparative genomics and genetic experiments were used to identify the causative DNA polymorphism. A W428R substitution near the active site of penicillin binding protein B1 (PBPB1) was identified as the cause of reduced ampicillin, amoxicillin and meropenem susceptibility. Further clinical L. monocytogenes isolates with similar susceptibility profiles were found by searching the genome database of the German consultant laboratory for Listeria for pbpB1 W428R-positive isolates. Spontaneous suppressors of L. monocytogenes reference strain EGD-e with reduced β-lactam susceptibility were selected during ampicillin exposure and their genomes were sequenced. The same pbpB1 mutation emerged in strain EGD-e during cultivation in the presence of ampicillin. Further experiments showed that meropenem also promotes the development of resistant suppressor mutants with pbpB1 mutations. Our work demonstrates that β-lactam susceptibility of L. monocytogenes can be reduced through specific substitutions in PBPB1. These mutations are potentially selected for during β-lactam treatment.
Insights
A specific mutation in penicillin binding protein B1 (PBPB1) reduces Listeria monocytogenes susceptibility to beta-lactam antibiotics like ampicillin. This PBPB1 W428R substitution can emerge during antibiotic treatment.
Area of Science:
- Infectious Diseases
- Microbiology
- Genetics
Background:
- Listeriosis, a severe foodborne illness, has high mortality rates.
- Current treatments for listeriosis include ampicillin, amoxicillin, penicillin, and gentamicin, with occasional use of meropenem.
- Beta-lactam resistant Listeria monocytogenes isolates are rare, and their resistance mechanisms are largely unknown.
Purpose of the Study:
- To identify the genetic basis of reduced beta-lactam susceptibility in a clinical Listeria monocytogenes isolate.
- To investigate the potential for beta-lactam antibiotics to select for resistant Listeria monocytogenes strains.
Main Methods:
- Resistance profiling of a clinical Listeria monocytogenes isolate.
- Whole genome sequencing and comparative genomics.
- Genetic experiments to confirm the role of identified mutations.
Main Results:
- A W428R substitution in penicillin binding protein B1 (PBPB1) was identified as the cause of reduced susceptibility to ampicillin, amoxicillin, and meropenem.
- The pbpB1 W428R mutation was found in other clinical isolates and emerged spontaneously in laboratory strains during exposure to ampicillin and meropenem.
- This specific PBPB1 mutation is potentially selected for during beta-lactam treatment.
Conclusions:
- Beta-lactam susceptibility in Listeria monocytogenes can be reduced by a specific substitution (W428R) in PBPB1.
- The emergence of this mutation suggests a potential mechanism for resistance development during antibiotic therapy for listeriosis.
- This finding has implications for monitoring and treating listeriosis, particularly in patients receiving beta-lactam antibiotics.
