Variation in colonization, ADP-ribosylating and vacuolating cytotoxin, and pulmonary disease severity among Mycoplasma pneumoniae strains

Chonnamet Techasaensiri, Claudia Tagliabue, Marianna Cagle, Pooya Iranpour, Kathy Katz, Thirumalai R. Kannan, Jacqueline J. Coalson, Joel B. Baseman, R. Doug Hardy

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Rationale: 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. Objectives: 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. Measurements and Main 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.

Original languageEnglish
Pages (from-to)797-804
Number of pages8
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume182
Issue number6
DOIs
Publication statusPublished - Sep 15 2010

Fingerprint

Mycoplasma pneumoniae
Cytotoxins
Adenosine Diphosphate
Lung Diseases
Lung
Bronchoalveolar Lavage
Macrophage Inflammatory Proteins
Polymerase Chain Reaction
Interleukin-12
Interleukin-1
Chemokines
Respiratory Tract Infections
Pneumonia
Theoretical Models
Cytokines

Keywords

  • ADP-ribosylating
  • Asthma
  • Mycoplasma pneumoniae
  • Pneumonia
  • Toxin

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Variation in colonization, ADP-ribosylating and vacuolating cytotoxin, and pulmonary disease severity among Mycoplasma pneumoniae strains. / Techasaensiri, Chonnamet; Tagliabue, Claudia; Cagle, Marianna; Iranpour, Pooya; Katz, Kathy; Kannan, Thirumalai R.; Coalson, Jacqueline J.; Baseman, Joel B.; Hardy, R. Doug.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 182, No. 6, 15.09.2010, p. 797-804.

Research output: Contribution to journalArticle

Techasaensiri, Chonnamet ; Tagliabue, Claudia ; Cagle, Marianna ; Iranpour, Pooya ; Katz, Kathy ; Kannan, Thirumalai R. ; Coalson, Jacqueline J. ; Baseman, Joel B. ; Hardy, R. Doug. / Variation in colonization, ADP-ribosylating and vacuolating cytotoxin, and pulmonary disease severity among Mycoplasma pneumoniae strains. In: American Journal of Respiratory and Critical Care Medicine. 2010 ; Vol. 182, No. 6. pp. 797-804.
@article{0b5caedeade040ffb416deacf8ae3fe8,
title = "Variation in colonization, ADP-ribosylating and vacuolating cytotoxin, and pulmonary disease severity among Mycoplasma pneumoniae strains",
abstract = "Rationale: 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. Objectives: 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. Measurements and Main 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.",
keywords = "ADP-ribosylating, Asthma, Mycoplasma pneumoniae, Pneumonia, Toxin",
author = "Chonnamet Techasaensiri and Claudia Tagliabue and Marianna Cagle and Pooya Iranpour and Kathy Katz and Kannan, {Thirumalai R.} and Coalson, {Jacqueline J.} and Baseman, {Joel B.} and Hardy, {R. Doug}",
year = "2010",
month = "9",
day = "15",
doi = "10.1164/rccm.201001-0080OC",
language = "English",
volume = "182",
pages = "797--804",
journal = "American Journal of Respiratory and Critical Care Medicine",
issn = "1073-449X",
publisher = "American Thoracic Society - AJRCCM",
number = "6",

}

TY - JOUR

T1 - Variation in colonization, ADP-ribosylating and vacuolating cytotoxin, and pulmonary disease severity among Mycoplasma pneumoniae strains

AU - Techasaensiri, Chonnamet

AU - Tagliabue, Claudia

AU - Cagle, Marianna

AU - Iranpour, Pooya

AU - Katz, Kathy

AU - Kannan, Thirumalai R.

AU - Coalson, Jacqueline J.

AU - Baseman, Joel B.

AU - Hardy, R. Doug

PY - 2010/9/15

Y1 - 2010/9/15

N2 - Rationale: 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. Objectives: 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. Measurements and Main 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.

AB - Rationale: 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. Objectives: 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. Measurements and Main 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.

KW - ADP-ribosylating

KW - Asthma

KW - Mycoplasma pneumoniae

KW - Pneumonia

KW - Toxin

UR - http://www.scopus.com/inward/record.url?scp=77957040139&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77957040139&partnerID=8YFLogxK

U2 - 10.1164/rccm.201001-0080OC

DO - 10.1164/rccm.201001-0080OC

M3 - Article

VL - 182

SP - 797

EP - 804

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

SN - 1073-449X

IS - 6

ER -