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An altered immune response, but not individual cationic antimicrobial peptides, is associated with the oral attenuation of Ara4N-deficient Salmonella enterica serovar Typhimurium in mice.
PLoS One. 2012; 7(11):e49588.Plos

Abstract

Salmonella enterica serovar Typhimurium (S. Typhimurium) uses two-component regulatory systems (TCRS) to respond to stimuli in the local microenvironment. Upon infection, the Salmonella TCRSs PhoP-PhoQ (PhoPQ) and PmrA-PmrB (PmrAB) are activated by environmental signals in the intestinal lumen and within host cells. TCRS-mediated gene expression results in lipopolysaccharide (LPS) modification and cationic antimicrobial peptide resistance. The PmrA-regulated pmrHFIJKLM operon mediates 4-amino-4-deoxy-L-arabinose (Ara4N) production and attachment to the lipid A of LPS. A ΔpmrF S. Typhimurium strain cannot produce Ara4N, exhibits increased sensitivity to cationic antimicrobial peptide (CAMP)-mediated killing, and attenuated virulence in mice upon oral infection. CAMPs are predicted to play a role in elimination of Salmonella, and may activate PhoPQ and PmrAB in vivo, which could increase bacterial resistance to host defenses. Competition experiments between wild type (WT) and ΔpmrF mutant strains of S. Typhimurium indicated that selection against this mutant first occurs within the intestinal lumen early during infection. However, CRAMP and active cryptdins alone are not responsible for elimination of Ara4N-deficient bacteria in vivo. Investigation into the early immune response to ΔpmrF showed that it differed slightly from the early immune response to WT S. Typhimurium. Further investigation into the early immune response to infection of Peyer's patches suggests a role for IL-13 in the attenution of the ΔpmrF mutant strain. Thus, prominent CAMPs present in the mouse intestine are not responsible for the selection against the ΔpmrF strain in this location, but limited alterations in innate immune induction were observed that affect bacterial survival and virulence.

Authors+Show Affiliations

Center for Microbial Interface Biology, The Ohio State University, Columbus, Ohio, United States of America.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23166721

Citation

Strandberg, Kristi L., et al. "An Altered Immune Response, but Not Individual Cationic Antimicrobial Peptides, Is Associated With the Oral Attenuation of Ara4N-deficient Salmonella Enterica Serovar Typhimurium in Mice." PloS One, vol. 7, no. 11, 2012, pp. e49588.
Strandberg KL, Richards SM, Tamayo R, et al. An altered immune response, but not individual cationic antimicrobial peptides, is associated with the oral attenuation of Ara4N-deficient Salmonella enterica serovar Typhimurium in mice. PLoS One. 2012;7(11):e49588.
Strandberg, K. L., Richards, S. M., Tamayo, R., Reeves, L. T., & Gunn, J. S. (2012). An altered immune response, but not individual cationic antimicrobial peptides, is associated with the oral attenuation of Ara4N-deficient Salmonella enterica serovar Typhimurium in mice. PloS One, 7(11), e49588. https://doi.org/10.1371/journal.pone.0049588
Strandberg KL, et al. An Altered Immune Response, but Not Individual Cationic Antimicrobial Peptides, Is Associated With the Oral Attenuation of Ara4N-deficient Salmonella Enterica Serovar Typhimurium in Mice. PLoS One. 2012;7(11):e49588. PubMed PMID: 23166721.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - An altered immune response, but not individual cationic antimicrobial peptides, is associated with the oral attenuation of Ara4N-deficient Salmonella enterica serovar Typhimurium in mice. AU - Strandberg,Kristi L, AU - Richards,Susan M, AU - Tamayo,Rita, AU - Reeves,Linh T, AU - Gunn,John S, Y1 - 2012/11/15/ PY - 2012/08/24/received PY - 2012/10/10/accepted PY - 2012/11/21/entrez PY - 2012/11/21/pubmed PY - 2013/6/21/medline SP - e49588 EP - e49588 JF - PloS one JO - PLoS One VL - 7 IS - 11 N2 - Salmonella enterica serovar Typhimurium (S. Typhimurium) uses two-component regulatory systems (TCRS) to respond to stimuli in the local microenvironment. Upon infection, the Salmonella TCRSs PhoP-PhoQ (PhoPQ) and PmrA-PmrB (PmrAB) are activated by environmental signals in the intestinal lumen and within host cells. TCRS-mediated gene expression results in lipopolysaccharide (LPS) modification and cationic antimicrobial peptide resistance. The PmrA-regulated pmrHFIJKLM operon mediates 4-amino-4-deoxy-L-arabinose (Ara4N) production and attachment to the lipid A of LPS. A ΔpmrF S. Typhimurium strain cannot produce Ara4N, exhibits increased sensitivity to cationic antimicrobial peptide (CAMP)-mediated killing, and attenuated virulence in mice upon oral infection. CAMPs are predicted to play a role in elimination of Salmonella, and may activate PhoPQ and PmrAB in vivo, which could increase bacterial resistance to host defenses. Competition experiments between wild type (WT) and ΔpmrF mutant strains of S. Typhimurium indicated that selection against this mutant first occurs within the intestinal lumen early during infection. However, CRAMP and active cryptdins alone are not responsible for elimination of Ara4N-deficient bacteria in vivo. Investigation into the early immune response to ΔpmrF showed that it differed slightly from the early immune response to WT S. Typhimurium. Further investigation into the early immune response to infection of Peyer's patches suggests a role for IL-13 in the attenution of the ΔpmrF mutant strain. Thus, prominent CAMPs present in the mouse intestine are not responsible for the selection against the ΔpmrF strain in this location, but limited alterations in innate immune induction were observed that affect bacterial survival and virulence. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/23166721/An_altered_immune_response_but_not_individual_cationic_antimicrobial_peptides_is_associated_with_the_oral_attenuation_of_Ara4N_deficient_Salmonella_enterica_serovar_Typhimurium_in_mice_ L2 - https://dx.plos.org/10.1371/journal.pone.0049588 DB - PRIME DP - Unbound Medicine ER -