Mutational Analysis of the Chlamydia muridarum Plasticity Zone.
Pathogenically diverse Chlamydia spp. can have surprisingly similar genomes. Chlamydia trachomatis isolates that cause trachoma, sexually transmitted genital tract infections (chlamydia), and invasive lymphogranuloma venereum (LGV) and the murine strain Chlamydia muridarum share 99% of their gene content. A region of high genomic diversity between Chlamydia spp. termed the plasticity zone (PZ) may encode niche-specific virulence determinants that dictate pathogenic diversity. We hypothesized that PZ genes might mediate the greater virulence and gamma interferon (IFN-γ) resistance of C. muridarum compared to C. trachomatis in the murine genital tract. To test this hypothesis, we isolated and characterized a series of C. muridarum PZ nonsense mutants. Strains with nonsense mutations in chlamydial cytotoxins, guaBA-add, and a phospholipase D homolog developed normally in cell culture. Two of the cytotoxin mutants were less cytotoxic than the wild type, suggesting that the cytotoxins may be functional. However, none of the PZ nonsense mutants exhibited increased IFN-γ sensitivity in cell culture or were profoundly attenuated in a murine genital tract infection model. Our results suggest that C. muridarum PZ genes are transcribed--and some may produce functional proteins--but are dispensable for infection of the murine genital tract.
Department of Biology, Indiana University, Bloomington, Indiana, USA.
Krithika
K
Rajaram
Department of Biology, Indiana University, Bloomington, Indiana, USA.
Amanda M
AM
Giebel
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Evelyn
E
Toh
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Shuai
S
Hu
Department of Biochemistry and Molecular Biology, Indiana University, Bloomington, Indiana, USA.
Jasmine H
JH
Newman
Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Sandra G
SG
Morrison
Laboratory of Intracellular Parasites, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.
Laszlo
L
Kari
Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Richard P
http://orcid.org/0000-0002-9747-9884
RP
Morrison
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA nelsonde@indiana.edu.
David E
DE
Nelson
D000818:Animals; D002690:Chlamydia Infections / Q000382:microbiology* / Q000473:pathology; D023502:Chlamydia muridarum / Q000235:genetics* / Q000502:physiology*; D002692:Chlamydia trachomatis / Q000235:genetics / Q000502:physiology; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005260:Female; D016680:Genome, Bacterial; D008810:Mice, Inbred C57BL; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics*
D018389:Codon, Nonsense; D037521:Virulence Factors