Pseudomonas aeruginosa Alters Peptidoglycan Composition under Nutrient Conditions Resembling Cystic Fibrosis Lung Infections
ABSTRACT Epidemic strains of Pseudomonas aeruginosa are highly virulent opportunistic pathogens with increased transmissibility and enhanced antimicrobial resistance. Understanding the cellular mechanisms behind this heightened virulence and resistance is critical. Peptidoglycan (PG) is an integral...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2022-06-01
|
| Series: | mSystems |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/msystems.00156-22 |
| _version_ | 1811342694586253312 |
|---|---|
| author | Erin M. Anderson Neethu Shaji Saji Alexander C. Anderson Dyanne Brewer Anthony J. Clarke Cezar M. Khursigara |
| author_facet | Erin M. Anderson Neethu Shaji Saji Alexander C. Anderson Dyanne Brewer Anthony J. Clarke Cezar M. Khursigara |
| author_sort | Erin M. Anderson |
| collection | DOAJ |
| description | ABSTRACT Epidemic strains of Pseudomonas aeruginosa are highly virulent opportunistic pathogens with increased transmissibility and enhanced antimicrobial resistance. Understanding the cellular mechanisms behind this heightened virulence and resistance is critical. Peptidoglycan (PG) is an integral component of P. aeruginosa cells that is essential to its survival and a target for antimicrobials. Here, we examined the global PG composition of two P. aeruginosa epidemic strains, LESB58 and LESlike1, and compared them to the common laboratory strains PAO1 and PA14. We also examined changes in PG composition when the strains were cultured under nutrient conditions that resembled cystic fibrosis lung infections. We identified 448 unique muropeptides and provide the first evidence for stem peptides modified with O-methylation, meso-diaminopimelic acid (mDAP) deamination, and novel substitutions of mDAP residues within P. aeruginosa PG. Our results also present the first evidence for both d,l- and l,d-endopeptidase activity on the PG sacculus of a Gram-negative organism. The PG composition of the epidemic strains varied significantly when grown under conditions resembling cystic fibrosis (CF) lung infections, showing increases in O-methylated stem peptides and decreases in l,d-endopeptidase activity as well as an increased abundance of de-N-acetylated sugars and l,d-transpeptidase activity, which are related to bacterial virulence and antibiotic resistance, respectively. We also identified strain-specific changes where LESlike1 increased the addition of unique amino acids to the terminus of the stem peptide and LESB58 increased amidase activity. Overall, this study demonstrates that P. aeruginosa PG composition is primarily influenced by nutrient conditions that mimic the CF lung; however, inherent strain-to-strain differences also exist. IMPORTANCE Using peptidoglycomics to examine the global composition of the peptidoglycan (PG) allows insights into the enzymatic activity that functions on this important biopolymer. Changes within the PG structure have implications for numerous physiological processes, including virulence and antimicrobial resistance. The identification of highly unique PG modifications illustrates the complexity of this biopolymer in Pseudomonas aeruginosa. Analyzing the PG composition of clinical P. aeruginosa epidemic strains provides insights into the increased virulence and antimicrobial resistance of these difficult-to-eradicate infections. |
| first_indexed | 2024-04-13T19:15:24Z |
| format | Article |
| id | doaj.art-22a4554b002542b5936eaefba2f65226 |
| institution | Directory Open Access Journal |
| issn | 2379-5077 |
| language | English |
| last_indexed | 2024-04-13T19:15:24Z |
| publishDate | 2022-06-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSystems |
| spelling | doaj.art-22a4554b002542b5936eaefba2f652262022-12-22T02:33:41ZengAmerican Society for MicrobiologymSystems2379-50772022-06-017310.1128/msystems.00156-22Pseudomonas aeruginosa Alters Peptidoglycan Composition under Nutrient Conditions Resembling Cystic Fibrosis Lung InfectionsErin M. Anderson0Neethu Shaji Saji1Alexander C. Anderson2Dyanne Brewer3Anthony J. Clarke4Cezar M. Khursigara5Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, CanadaDepartment of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, CanadaDepartment of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, CanadaMass Spectrometry Facility, University of Guelph, Guelph, Ontario, CanadaDepartment of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, CanadaDepartment of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, CanadaABSTRACT Epidemic strains of Pseudomonas aeruginosa are highly virulent opportunistic pathogens with increased transmissibility and enhanced antimicrobial resistance. Understanding the cellular mechanisms behind this heightened virulence and resistance is critical. Peptidoglycan (PG) is an integral component of P. aeruginosa cells that is essential to its survival and a target for antimicrobials. Here, we examined the global PG composition of two P. aeruginosa epidemic strains, LESB58 and LESlike1, and compared them to the common laboratory strains PAO1 and PA14. We also examined changes in PG composition when the strains were cultured under nutrient conditions that resembled cystic fibrosis lung infections. We identified 448 unique muropeptides and provide the first evidence for stem peptides modified with O-methylation, meso-diaminopimelic acid (mDAP) deamination, and novel substitutions of mDAP residues within P. aeruginosa PG. Our results also present the first evidence for both d,l- and l,d-endopeptidase activity on the PG sacculus of a Gram-negative organism. The PG composition of the epidemic strains varied significantly when grown under conditions resembling cystic fibrosis (CF) lung infections, showing increases in O-methylated stem peptides and decreases in l,d-endopeptidase activity as well as an increased abundance of de-N-acetylated sugars and l,d-transpeptidase activity, which are related to bacterial virulence and antibiotic resistance, respectively. We also identified strain-specific changes where LESlike1 increased the addition of unique amino acids to the terminus of the stem peptide and LESB58 increased amidase activity. Overall, this study demonstrates that P. aeruginosa PG composition is primarily influenced by nutrient conditions that mimic the CF lung; however, inherent strain-to-strain differences also exist. IMPORTANCE Using peptidoglycomics to examine the global composition of the peptidoglycan (PG) allows insights into the enzymatic activity that functions on this important biopolymer. Changes within the PG structure have implications for numerous physiological processes, including virulence and antimicrobial resistance. The identification of highly unique PG modifications illustrates the complexity of this biopolymer in Pseudomonas aeruginosa. Analyzing the PG composition of clinical P. aeruginosa epidemic strains provides insights into the increased virulence and antimicrobial resistance of these difficult-to-eradicate infections.https://journals.asm.org/doi/10.1128/msystems.00156-22Pseudomonas aeruginosapeptidoglycanLiverpool epidemic strainpeptidoglycomicsantibiotic resistance |
| spellingShingle | Erin M. Anderson Neethu Shaji Saji Alexander C. Anderson Dyanne Brewer Anthony J. Clarke Cezar M. Khursigara Pseudomonas aeruginosa Alters Peptidoglycan Composition under Nutrient Conditions Resembling Cystic Fibrosis Lung Infections mSystems Pseudomonas aeruginosa peptidoglycan Liverpool epidemic strain peptidoglycomics antibiotic resistance |
| title | Pseudomonas aeruginosa Alters Peptidoglycan Composition under Nutrient Conditions Resembling Cystic Fibrosis Lung Infections |
| title_full | Pseudomonas aeruginosa Alters Peptidoglycan Composition under Nutrient Conditions Resembling Cystic Fibrosis Lung Infections |
| title_fullStr | Pseudomonas aeruginosa Alters Peptidoglycan Composition under Nutrient Conditions Resembling Cystic Fibrosis Lung Infections |
| title_full_unstemmed | Pseudomonas aeruginosa Alters Peptidoglycan Composition under Nutrient Conditions Resembling Cystic Fibrosis Lung Infections |
| title_short | Pseudomonas aeruginosa Alters Peptidoglycan Composition under Nutrient Conditions Resembling Cystic Fibrosis Lung Infections |
| title_sort | pseudomonas aeruginosa alters peptidoglycan composition under nutrient conditions resembling cystic fibrosis lung infections |
| topic | Pseudomonas aeruginosa peptidoglycan Liverpool epidemic strain peptidoglycomics antibiotic resistance |
| url | https://journals.asm.org/doi/10.1128/msystems.00156-22 |
| work_keys_str_mv | AT erinmanderson pseudomonasaeruginosaalterspeptidoglycancompositionundernutrientconditionsresemblingcysticfibrosislunginfections AT neethushajisaji pseudomonasaeruginosaalterspeptidoglycancompositionundernutrientconditionsresemblingcysticfibrosislunginfections AT alexandercanderson pseudomonasaeruginosaalterspeptidoglycancompositionundernutrientconditionsresemblingcysticfibrosislunginfections AT dyannebrewer pseudomonasaeruginosaalterspeptidoglycancompositionundernutrientconditionsresemblingcysticfibrosislunginfections AT anthonyjclarke pseudomonasaeruginosaalterspeptidoglycancompositionundernutrientconditionsresemblingcysticfibrosislunginfections AT cezarmkhursigara pseudomonasaeruginosaalterspeptidoglycancompositionundernutrientconditionsresemblingcysticfibrosislunginfections |