Chancroid pathophysiology: Difference between revisions
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===Pathogenesis=== | ===Pathogenesis=== | ||
*''H. ducreyi'' enters the skin through breaks in the epithelium. | *''H. ducreyi'' enters the skin through breaks in the epithelium. | ||
*''H. ducreyi'' produces 3 fimbrialike proteins (Flp), Flp1, Flp2, and Flp3 | *''H. ducreyi'' produces 3 fimbrialike proteins (Flp), Flp1, Flp2, and Flp3 that help the bacteria adhere to subcutaneous epithelial cells and fibroblasts.<ref name="SpinolaFortney2003">{{cite journal|last1=Spinola|first1=S. M.|last2=Fortney|first2=K. R.|last3=Katz|first3=B. P.|last4=Latimer|first4=J. L.|last5=Mock|first5=J. R.|last6=Vakevainen|first6=M.|last7=Hansen|first7=E. J.|title=Haemophilus ducreyi Requires an Intact flp Gene Cluster for Virulence in Humans|journal=Infection and Immunity|volume=71|issue=12|year=2003|pages=7178–7182|issn=0019-9567|doi=10.1128/IAI.71.12.7178-7182.2003}}</ref><ref name="pmid1391058">{{cite journal| author=Abeck D, Johnson AP| title=Pathophysiological concept of Haemophilus ducreyi infection (chancroid) | journal=Int J STD AIDS | year= 1992 | volume= 3 | issue= 5 | pages= 319-23 | pmid=1391058 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1391058}}</ref> | ||
*''H. ducreyi'' recruits inflammatory cells to the infected area and induces secretion of interleukin 6 (IL-6) and interleukin 8 (IL-8) from epithelial cells. IL-8 induces neutrophils and macrophages to form abscesses, which may cause the presentation of erythematous papules which progress into intradermal pustules.<ref name="pmid1391058"></ref><ref name="ChancroidWikipedia">Chancroid. Wikipedia (July 16, 2015). https://en.wikipedia.org/wiki/Chancroid Accessed on January 6, 2016.</ref><ref name="ChancroidMedscape">Chancroid in Emergency Medicine. Medscape (February 12, 2014). http://emedicine.medscape.com/article/781520-overview#a5 Accessed January 8, 2016.</ref> | *''H. ducreyi'' recruits inflammatory cells to the infected area and induces secretion of interleukin 6 (IL-6) and interleukin 8 (IL-8) from epithelial cells. IL-8 induces neutrophils and macrophages to form abscesses, which may cause the presentation of erythematous papules which progress into intradermal pustules.<ref name="pmid1391058"></ref><ref name="ChancroidWikipedia">Chancroid. Wikipedia (July 16, 2015). https://en.wikipedia.org/wiki/Chancroid Accessed on January 6, 2016.</ref><ref name="ChancroidMedscape">Chancroid in Emergency Medicine. Medscape (February 12, 2014). http://emedicine.medscape.com/article/781520-overview#a5 Accessed January 8, 2016.</ref> | ||
*Ulcers develop after secretion of the virulence factor ''H. ducreyi'' cytolethal distending toxin (HdCDT), which causes necrosis of myeloid and epithelial cells.<ref name="ChancroidMedscape"></ref> | *Ulcers develop after secretion of the virulence factor ''H. ducreyi'' cytolethal distending toxin (HdCDT), which causes necrosis of myeloid and epithelial cells.<ref name="ChancroidMedscape"></ref> | ||
| Line 20: | Line 20: | ||
====Virulence Factors==== | ====Virulence Factors==== | ||
*''H. Ducreyi'' produces and secretes 2 major virulence factors: | *''H. Ducreyi'' produces and secretes 2 major virulence factors: fimbrialike protein (Flp) and ''H. ducreyi'' cytolethal distending toxin (HdCDT). | ||
::'''Flp''': | |||
::*A 12.8 kb Flp operon regulates the expression of 3 fimbrialike proteins, Flp1, Flp2, and Flp3 in a type IV secretion system. These proteins have been demonstrated to play an important role in adherence to fibroblasts and pathogenesis of chancroid.<ref name="SpinolaFortney2003"></ref> | |||
::'''HdCDT''':<ref name="FrisanCortes-Bratti2003">{{cite journal|last1=Frisan|first1=Teresa|last2=Cortes-Bratti|first2=Ximena|last3=Chaves-Olarte|first3=Esteban|last4=Stenerlow|first4=Bo|last5=Thelestam|first5=Monica|title=The Haemophilus ducreyi cytolethal distending toxin induces DNA double-strand breaks and promotes ATM-dependent activation of RhoA|journal=Cellular Microbiology|volume=5|issue=10|year=2003|pages=695–707|issn=1462-5814|doi=10.1046/j.1462-5822.2003.00311.x}}</ref> | |||
::*HdCDT is a tripartite protein complex consisting of CdtA, CdtB, and CdtC subunits, all of which are required to produce the active form of the toxin. | |||
::*HdCDT induces DNA double-stranded breaks that result in cellular responses similar to ionizing radiation. | |||
::*The effect of HdCDT is cell type-specific. | |||
::*In epithelial cells and fibroblasts, DNA damage activates ATM kinases, which activate RhoA GTPase leading to induction of actin stress fibers and cell distention. This response arrests the cell cycle, resulting in delayed healing. | |||
::*RhoA activation is not detected in lymphocytes, leading to apoptosis of B and T cell lines. | |||
==References== | ==References== | ||
Revision as of 20:54, 11 January 2016
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yazan Daaboul, M.D.; Nate Michalak, B.A.; Serge Korjian M.D.
Overview
Pathophysiology
Transmission
- Chancroid may develop after transmission of class I or class II of the bacterium Haemophilus ducreyi through sexual contact.[1]
- A class I gentically distinct subclade strain of H. ducreyi may serve as the etiologic agent of non-sexually transmitted skin ulcers.[2][3]
Pathogenesis
- H. ducreyi enters the skin through breaks in the epithelium.
- H. ducreyi produces 3 fimbrialike proteins (Flp), Flp1, Flp2, and Flp3 that help the bacteria adhere to subcutaneous epithelial cells and fibroblasts.[4][5]
- H. ducreyi recruits inflammatory cells to the infected area and induces secretion of interleukin 6 (IL-6) and interleukin 8 (IL-8) from epithelial cells. IL-8 induces neutrophils and macrophages to form abscesses, which may cause the presentation of erythematous papules which progress into intradermal pustules.[5][6][7]
- Ulcers develop after secretion of the virulence factor H. ducreyi cytolethal distending toxin (HdCDT), which causes necrosis of myeloid and epithelial cells.[7]
- It is presumed that iron plays an essential role in chancroid pathogenesis.[5]
- H. ducreyi has the ability to avoid phagocytosis.[7]
Virulence Factors
- H. Ducreyi produces and secretes 2 major virulence factors: fimbrialike protein (Flp) and H. ducreyi cytolethal distending toxin (HdCDT).
- Flp:
- A 12.8 kb Flp operon regulates the expression of 3 fimbrialike proteins, Flp1, Flp2, and Flp3 in a type IV secretion system. These proteins have been demonstrated to play an important role in adherence to fibroblasts and pathogenesis of chancroid.[4]
- HdCDT:[8]
- HdCDT is a tripartite protein complex consisting of CdtA, CdtB, and CdtC subunits, all of which are required to produce the active form of the toxin.
- HdCDT induces DNA double-stranded breaks that result in cellular responses similar to ionizing radiation.
- The effect of HdCDT is cell type-specific.
- In epithelial cells and fibroblasts, DNA damage activates ATM kinases, which activate RhoA GTPase leading to induction of actin stress fibers and cell distention. This response arrests the cell cycle, resulting in delayed healing.
- RhoA activation is not detected in lymphocytes, leading to apoptosis of B and T cell lines.
- Flp:
References
- ↑ Chancroid. MedlinePlus (Decemner 2, 2015). https://www.nlm.nih.gov/medlineplus/ency/article/000635.htm Accessed January 6, 2015.
- ↑ Marks M, Chi KH, Vahi V, Pillay A, Sokana O, Pavluck A; et al. (2014). "Haemophilus ducreyi associated with skin ulcers among children, Solomon Islands". Emerg Infect Dis. 20 (10): 1705–7. doi:10.3201/eid2010.140573. PMC 4193279. PMID 25271477.
- ↑ Gaston JR, Roberts SA, Humphreys TL (2015). "Molecular phylogenetic analysis of non-sexually transmitted strains of Haemophilus ducreyi". PLoS One. 10 (3): e0118613. doi:10.1371/journal.pone.0118613. PMC 4361675. PMID 25774793.
- ↑ 4.0 4.1 Spinola, S. M.; Fortney, K. R.; Katz, B. P.; Latimer, J. L.; Mock, J. R.; Vakevainen, M.; Hansen, E. J. (2003). "Haemophilus ducreyi Requires an Intact flp Gene Cluster for Virulence in Humans". Infection and Immunity. 71 (12): 7178–7182. doi:10.1128/IAI.71.12.7178-7182.2003. ISSN 0019-9567.
- ↑ 5.0 5.1 5.2 Abeck D, Johnson AP (1992). "Pathophysiological concept of Haemophilus ducreyi infection (chancroid)". Int J STD AIDS. 3 (5): 319–23. PMID 1391058.
- ↑ Chancroid. Wikipedia (July 16, 2015). https://en.wikipedia.org/wiki/Chancroid Accessed on January 6, 2016.
- ↑ 7.0 7.1 7.2 Chancroid in Emergency Medicine. Medscape (February 12, 2014). http://emedicine.medscape.com/article/781520-overview#a5 Accessed January 8, 2016.
- ↑ Frisan, Teresa; Cortes-Bratti, Ximena; Chaves-Olarte, Esteban; Stenerlow, Bo; Thelestam, Monica (2003). "The Haemophilus ducreyi cytolethal distending toxin induces DNA double-strand breaks and promotes ATM-dependent activation of RhoA". Cellular Microbiology. 5 (10): 695–707. doi:10.1046/j.1462-5822.2003.00311.x. ISSN 1462-5814.