Variation in colonization, ADP-ribosylating and vacuolating cytotoxin, and pulmonary disease severity among mycoplasma pneumoniae strains.
BACKGROUND
Mycoplasma pneumoniae was recently discovered to produce an ADP-ribosylating and vacuolating cytotoxin, designated CARDS toxin, which is hypothesized to be a primary pathogenic mechanism responsible for M. pneumoniae-induced pulmonary inflammation. It is unknown if cytotoxin production varies with M. pneumoniae strain or if variation in cytotoxin production affects pulmonary disease severity.


OBJECTIVE
To examine the production of CARDS toxin by various strains of M. pneumoniae and compare the disease manifestations elicited by these strains in an experimental model of M. pneumoniae respiratory infection.


METHODS
BALB/c mice were inoculated once intranasally with SP4 broth (negative control) or three different M. pneumoniae strains: M129-B7, M129-B9, or S1. Mice were assessed at 1, 2, 4, 7, 10, and 14 days after inoculation. Outcome variables included comparisons among M. pneumoniae strains relative to bronchoalveolar lavage (BAL) M. pneumoniae quantitative culture, CARDS toxin-based PCR, and CARDS toxin protein determinations, as well as cytokine and chemokine concentrations. Graded lung histopathologic score (HPS) was also assessed.


RESULTS
CARDS toxin concentrations were significantly increased in mice inoculated with strain S1 compared with mice inoculated with M129-B7 or M129-B9 strains. Quantitative M. pneumoniae culture and polymerase chain reaction were also significantly greater in mice infected with S1 strain compared with the other two strains, as were lung HPS and concentrations of IFN-γ, IL-12, IL-1α, macrophage inflammatory protein-1α, and keratinocyte-derived chemokine. In addition, a significant positive correlation was found between CARDS toxin concentration and lung HPS.


CONCLUSIONS
CARDS toxin concentrations in BAL are directly linked to the ability of specific M. pneumoniae strains to colonize, replicate, and persist, and elicit lung histopathology. This variation among strains may predict the range in severity of pulmonary disease observed among patients.
Techasaensiri
Chonnamet
C
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Tagliabue
Claudia
C
Cagle
Marianna
M
Iranpour
Pooya
P
Katz
Kathy
K
Kannan
Thirumalai R
TR
Coalson
Jacqueline J
JJ
Baseman
Joel B
JB
Hardy
R Doug
RD
D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D001427:Bacterial Toxins / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D015169:Colony Count, Microbial; D003603:Cytotoxins / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D008171:Lung Diseases / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009177:Mycoplasma pneumoniae / Q000145:classification / Q000254:growth & development / Q000472:pathogenicity*; D011019:Pneumonia, Mycoplasma / Q000378:metabolism / Q000382:microbiology; D012720:Severity of Illness Index
D001426:Bacterial Proteins; D001427:Bacterial Toxins; C546120:CARDS toxin, Mycoplasma pneumoniae; D003603:Cytotoxins