Cross-talk among #flesheating #Aeromonas hydrophila #strains in mixed #infection leading to #necrotizing #fasciitis (Proc Natl Aca Sci USA, abstract)

[Source: Proceedings of the National Academy of Sciences of the United States of America, full page: (LINK). Abstract, edited.]

Cross-talk among flesh-eating Aeromonas hydrophila strains in mixed infection leading to necrotizing fasciitis [      ]

Duraisamy Ponnusamy ^a,¹, Elena V. Kozlova ^a,¹, Jian Sha ^a, Tatiana E. Erova ^a, Sasha R. Azar ^a, Eric C. Fitts ^a, Michelle L. Kirtley ^a, Bethany L. Tiner ^a, Jourdan A. Andersson ^a, Christopher J. Grim ^b, Richard P. Isom ^c, Nur A. Hasan ^c,^d, Rita R. Colwell ^c,^d,^e,², and Ashok K. Chopra ^a,²

Author Affiliations: ^aDepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555; ^bCenter for Food Safety and Applied Nutrition, Office of Applied Research and Safety Assessment, Food and Drug Administration, Laurel, MD 20708; ^cCosmosID Inc., Rockville, MD 20850; ^dCenter for Bioinformatics and Computational Biology, University of Maryland Institute for Advanced Computer Studies, University of Maryland, College Park, MD 20742; ^eBloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21205

Contributed by Rita R. Colwell, December 4, 2015 (sent for review October 6, 2015; reviewed by Joerg Graf, Brigitte Lamy, Mark R. Liles, and Jonathan G. Shaw)

 

Significance

Necrotizing fasciitis (NF) is a rapidly progressing fatal skin and muscle tissue lesion. We studied a human case of NF and found that the infection was caused by multiple strains of A. hydrophila (NF1–NF4). The latter three strains constitute a clonal group, whereas NF1 is phylogenetically distinct. We tested these strains individually in a mouse intramuscular model of infection and observed NF1 to be less virulent than NF2. However, when NF1 and NF2 were mixed, NF1 exhibited more virulence and it decreased NF2 virulence. The cross-talk between NF1 and NF2 was due to the presence of ExoA toxin in NF2, ability of NF1 and NF2 to differentially modulate innate immune mechanism(s), and direct killing of NF2 by NF1.

 

Abstract

Necrotizing fasciitis (NF) caused by flesh-eating bacteria is associated with high case fatality. In an earlier study, we reported infection of an immunocompetent individual with multiple strains of Aeromonas hydrophila (NF1–NF4), the latter three constituted a clonal group whereas NF1 was phylogenetically distinct. To understand the complex interactions of these strains in NF pathophysiology, a mouse model was used, whereby either single or mixed A. hydrophila strains were injected intramuscularly. NF2, which harbors exotoxin A (exoA) gene, was highly virulent when injected alone, but its virulence was attenuated in the presence of NF1 (exoA-minus). NF1 alone, although not lethal to animals, became highly virulent when combined with NF2, its virulence augmented by cis–exoA expression when injected alone in mice. Based on metagenomics and microbiological analyses, it was found that, in mixed infection, NF1 selectively disseminated to mouse peripheral organs, whereas the other strains (NF2, NF3, and NF4) were confined to the injection site and eventually cleared. In vitro studies showed NF2 to be more effectively phagocytized and killed by macrophages than NF1. NF1 inhibited growth of NF2 on solid media, but ExoA of NF2 augmented virulence of NF1 and the presence of NF1 facilitated clearance of NF2 from animals either by enhanced priming of host immune system or direct killing via a contact-dependent mechanism.

Aeromonas hydrophila – necrotizing fasciitis – mixed infections – intramuscular mouse model – metagenomics

 

Footnotes

¹D.P. and E.V.K. contributed equally to this work.

²To whom correspondence may be addressed. Email: rcolwell@umiacs.umd.edu or achopra@utmb.edu.

Author contributions: J.S., N.A.H., R.R.C., and A.K.C. designed research; D.P., E.V.K., T.E.E., S.R.A., E.C.F., M.L.K., B.L.T., J.A.A., and C.J.G. performed research; E.V.K., E.C.F., R.R.C., and A.K.C. contributed new reagents/analytic tools; D.P., E.V.K., C.J.G., R.P.I., and N.A.H. analyzed data; D.P., J.S., E.C.F., C.J.G., N.A.H., R.R.C., and A.K.C. wrote the paper; and R.R.C. and A.K.C. conceived the idea.

Reviewers: J.G., University of Connecticut; B.L., Universite de Montpellier; M.R.L., Auburn University; and J.G.S., University of Sheffield.

The authors declare no conflict of interest.

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1523817113/-/DCSupplemental.

http://www.pnas.org/preview_site/misc/userlicense.xhtml

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Keywords: Research; Abstracts; Necrotizing Fasciitis; Aeromonas hydrophila.

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