PMID- 35722306
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220818
IS  - 1664-302X (Print)
IS  - 1664-302X (Electronic)
IS  - 1664-302X (Linking)
VI  - 13
DP  - 2022
TI  - Identification and Functional Characterization of Peptides With Antimicrobial 
      Activity From the Syphilis Spirochete, Treponema pallidum.
PG  - 888525
LID - 10.3389/fmicb.2022.888525 [doi]
LID - 888525
AB  - The etiological agent of syphilis, Treponema pallidum ssp. pallidum, is a highly 
      invasive "stealth" pathogen that can evade the host immune response and persist 
      within the host for decades. This obligate human pathogen is adept at 
      establishing infection and surviving at sites within the host that have a 
      multitude of competing microbes, sometimes including pathogens. One survival 
      strategy employed by bacteria found at polymicrobial sites is elimination of 
      competing microorganisms by production of antimicrobial peptides (AMPs). 
      Antimicrobial peptides are low molecular weight proteins (miniproteins) that 
      function directly via inhibition and killing of microbes and/or indirectly via 
      modulation of the host immune response, which can facilitate immune evasion. In 
      the current study, we used bioinformatics to show that approximately 7% of the T. 
      pallidum proteome is comprised of miniproteins of 150 amino acids or less with 
      unknown functions. To investigate the possibility that AMP production is an 
      unrecognized defense strategy used by T. pallidum during infection, we developed 
      a bioinformatics pipeline to analyze the complement of T. pallidum miniproteins 
      of unknown function for the identification of potential AMPs. This analysis 
      identified 45 T. pallidum AMP candidates; of these, Tp0451a and Tp0749 were 
      subjected to further bioinformatic analyses to identify AMP critical core regions 
      (AMPCCRs). Four potential AMPCCRs from the two predicted AMPs were identified and 
      peptides corresponding to these AMPCCRs were experimentally confirmed to exhibit 
      bacteriostatic and bactericidal activity against a panel of biologically relevant 
      Gram-positive and Gram-negative bacteria. Immunomodulation assays performed under 
      inflammatory conditions demonstrated that one of the AMPCCRs was also capable of 
      differentially regulating expression of two pro-inflammatory chemokines [monocyte 
      chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8)]. These findings 
      demonstrate proof-of-concept for our developed AMP identification pipeline and 
      are consistent with the novel concept that T. pallidum expresses AMPs to defend 
      against competing microbes and modulate the host immune response.
CI  - Copyright (c) 2022 Houston, Schovanek, Conway, Mustafa, Gomez, Ramaswamy, Haimour, 
      Boulanger, Reynolds and Cameron.
FAU - Houston, Simon
AU  - Houston S
AD  - Department of Biochemistry and Microbiology, University of Victoria, Victoria, 
      BC, Canada.
FAU - Schovanek, Ethan
AU  - Schovanek E
AD  - Department of Biochemistry and Microbiology, University of Victoria, Victoria, 
      BC, Canada.
FAU - Conway, Kate M E
AU  - Conway KME
AD  - Department of Biochemistry and Microbiology, University of Victoria, Victoria, 
      BC, Canada.
FAU - Mustafa, Sarah
AU  - Mustafa S
AD  - Department of Biochemistry and Microbiology, University of Victoria, Victoria, 
      BC, Canada.
FAU - Gomez, Alloysius
AU  - Gomez A
AD  - Department of Biochemistry and Microbiology, University of Victoria, Victoria, 
      BC, Canada.
FAU - Ramaswamy, Raghavendran
AU  - Ramaswamy R
AD  - Department of Biochemistry and Microbiology, University of Victoria, Victoria, 
      BC, Canada.
FAU - Haimour, Ayman
AU  - Haimour A
AD  - Department of Biochemistry and Microbiology, University of Victoria, Victoria, 
      BC, Canada.
FAU - Boulanger, Martin J
AU  - Boulanger MJ
AD  - Department of Biochemistry and Microbiology, University of Victoria, Victoria, 
      BC, Canada.
FAU - Reynolds, Lisa A
AU  - Reynolds LA
AD  - Department of Biochemistry and Microbiology, University of Victoria, Victoria, 
      BC, Canada.
FAU - Cameron, Caroline E
AU  - Cameron CE
AD  - Department of Biochemistry and Microbiology, University of Victoria, Victoria, 
      BC, Canada.
AD  - Division of Allergy and Infectious Diseases, Department of Medicine, University 
      of Washington, Seattle, WA, United States.
LA  - eng
GR  - R01 AI051334/AI/NIAID NIH HHS/United States
GR  - R37 AI051334/AI/NIAID NIH HHS/United States
PT  - Journal Article
DEP - 20220503
PL  - Switzerland
TA  - Front Microbiol
JT  - Frontiers in microbiology
JID - 101548977
PMC - PMC9200625
OTO - NOTNLM
OT  - Treponema pallidum
OT  - antimicrobial peptides
OT  - bactericidal
OT  - bacteriostatic
OT  - syphilis
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/06/21 06:00
MHDA- 2022/06/21 06:01
PMCR- 2022/05/03
CRDT- 2022/06/20 04:07
PHST- 2022/03/03 00:00 [received]
PHST- 2022/04/08 00:00 [accepted]
PHST- 2022/06/20 04:07 [entrez]
PHST- 2022/06/21 06:00 [pubmed]
PHST- 2022/06/21 06:01 [medline]
PHST- 2022/05/03 00:00 [pmc-release]
AID - 10.3389/fmicb.2022.888525 [doi]
PST - epublish
SO  - Front Microbiol. 2022 May 3;13:888525. doi: 10.3389/fmicb.2022.888525. 
      eCollection 2022.