Salmonella Typhimurium PagP- and UgtL-dependent resistance to antimicrobial peptides contributes to the gut colonization.
Mucosal barrier formed by cationic antimicrobial peptides (CAMPs) is believed to be crucial for host protection from pathogenic gut infection. However, some pathogens can develop resistance to the CAMPs to survive in hosts. Salmonella enterica is a common cause of acute diarrhea. During the course o...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5739500?pdf=render |
| _version_ | 1818136516314005504 |
|---|---|
| author | Ryosuke Goto Tsuyoshi Miki Nao Nakamura Mayuka Fujimoto Nobuhiko Okada |
| author_facet | Ryosuke Goto Tsuyoshi Miki Nao Nakamura Mayuka Fujimoto Nobuhiko Okada |
| author_sort | Ryosuke Goto |
| collection | DOAJ |
| description | Mucosal barrier formed by cationic antimicrobial peptides (CAMPs) is believed to be crucial for host protection from pathogenic gut infection. However, some pathogens can develop resistance to the CAMPs to survive in hosts. Salmonella enterica is a common cause of acute diarrhea. During the course of this disease, the pathogen must continuously colonize the gut lumen, which contains CAMPs. However, it is incompletely understood whether the resistance of Salmonella strains to CAMPs contributes to the development of gut infections. PhoPQ two-component system-dependent lipid A modifications confer resistance to CAMPs in S. enterica serovar Typhimurium. Therefore, we introduced mutations into the PhoPQ-regulated genes in an S. Typhimurium strain, obtaining pagP ugtL and pmrA mutant strains. Each mutant strain demonstrated a distinct spectrum of the resistance to CAMPs. Using streptomycin mouse model for Salmonella diarrhea, we show that the pagP ugtL, but not pmrA, mutant strain had a gut colonization defect. Furthermore, the pagP ugtL, but not pmrA, mutant strain had decreased outer membrane integrity and susceptibility to magainin 2, an alpha-helical CAMP. Taken together, the PagP- and UgtL-dependent resistance to CAMPs was demonstrated to contribute to sustained colonization in the gut. This may be due to the robust outer membrane of S. Typhimurium, inducing the resistance to alpha-helical CAMPs such as α-defensins. Our findings indicate that the development of resistance to CAMPs is required for the S. Typhimurium gut infection. |
| first_indexed | 2024-12-11T09:41:39Z |
| format | Article |
| id | doaj.art-ed597804a89d4d85bfd7523a03f960c0 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T09:41:39Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ed597804a89d4d85bfd7523a03f960c02022-12-22T01:12:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-011212e019009510.1371/journal.pone.0190095Salmonella Typhimurium PagP- and UgtL-dependent resistance to antimicrobial peptides contributes to the gut colonization.Ryosuke GotoTsuyoshi MikiNao NakamuraMayuka FujimotoNobuhiko OkadaMucosal barrier formed by cationic antimicrobial peptides (CAMPs) is believed to be crucial for host protection from pathogenic gut infection. However, some pathogens can develop resistance to the CAMPs to survive in hosts. Salmonella enterica is a common cause of acute diarrhea. During the course of this disease, the pathogen must continuously colonize the gut lumen, which contains CAMPs. However, it is incompletely understood whether the resistance of Salmonella strains to CAMPs contributes to the development of gut infections. PhoPQ two-component system-dependent lipid A modifications confer resistance to CAMPs in S. enterica serovar Typhimurium. Therefore, we introduced mutations into the PhoPQ-regulated genes in an S. Typhimurium strain, obtaining pagP ugtL and pmrA mutant strains. Each mutant strain demonstrated a distinct spectrum of the resistance to CAMPs. Using streptomycin mouse model for Salmonella diarrhea, we show that the pagP ugtL, but not pmrA, mutant strain had a gut colonization defect. Furthermore, the pagP ugtL, but not pmrA, mutant strain had decreased outer membrane integrity and susceptibility to magainin 2, an alpha-helical CAMP. Taken together, the PagP- and UgtL-dependent resistance to CAMPs was demonstrated to contribute to sustained colonization in the gut. This may be due to the robust outer membrane of S. Typhimurium, inducing the resistance to alpha-helical CAMPs such as α-defensins. Our findings indicate that the development of resistance to CAMPs is required for the S. Typhimurium gut infection.http://europepmc.org/articles/PMC5739500?pdf=render |
| spellingShingle | Ryosuke Goto Tsuyoshi Miki Nao Nakamura Mayuka Fujimoto Nobuhiko Okada Salmonella Typhimurium PagP- and UgtL-dependent resistance to antimicrobial peptides contributes to the gut colonization. PLoS ONE |
| title | Salmonella Typhimurium PagP- and UgtL-dependent resistance to antimicrobial peptides contributes to the gut colonization. |
| title_full | Salmonella Typhimurium PagP- and UgtL-dependent resistance to antimicrobial peptides contributes to the gut colonization. |
| title_fullStr | Salmonella Typhimurium PagP- and UgtL-dependent resistance to antimicrobial peptides contributes to the gut colonization. |
| title_full_unstemmed | Salmonella Typhimurium PagP- and UgtL-dependent resistance to antimicrobial peptides contributes to the gut colonization. |
| title_short | Salmonella Typhimurium PagP- and UgtL-dependent resistance to antimicrobial peptides contributes to the gut colonization. |
| title_sort | salmonella typhimurium pagp and ugtl dependent resistance to antimicrobial peptides contributes to the gut colonization |
| url | http://europepmc.org/articles/PMC5739500?pdf=render |
| work_keys_str_mv | AT ryosukegoto salmonellatyphimuriumpagpandugtldependentresistancetoantimicrobialpeptidescontributestothegutcolonization AT tsuyoshimiki salmonellatyphimuriumpagpandugtldependentresistancetoantimicrobialpeptidescontributestothegutcolonization AT naonakamura salmonellatyphimuriumpagpandugtldependentresistancetoantimicrobialpeptidescontributestothegutcolonization AT mayukafujimoto salmonellatyphimuriumpagpandugtldependentresistancetoantimicrobialpeptidescontributestothegutcolonization AT nobuhikookada salmonellatyphimuriumpagpandugtldependentresistancetoantimicrobialpeptidescontributestothegutcolonization |