Synthesis and Distribution of CARDS Toxin During Mycoplasma pneumoniae Infection in a Murine Model

Abstract

Mice were infected with Mycoplasma pneumoniae and monitored for the synthesis and distribution of the unique adenosine diphosphate-ribosylating and vacuolating Community Acquired Respiratory Distress Syndrome (CARDS) toxin in bronchiolar lavage fluid (BALF) and lung. We noted direct relationships between the concentration of CARDS toxin and numbers of mycoplasma genomes in BALF and the degree of histologic pulmonary inflammation. Immunostaining of lungs revealed extensive colonization by mycoplasmas, including the detection of CARDS toxin in the corresponding inflamed airways. Lung lesion scores were higher during the early stages of infection, decreased gradually by day 14 postinfection, and reached substantially lower values at day 35. Infected mouse immunoglobulin (Ig) M and IgG titers were positive for CARDS toxin as well as for the major adhesin P1 of M. pneumoniae. These data reinforce the proposed pathogenic role of CARDS toxin in M. pneumoniae-mediated pathologies.

Mycoplasma pneumoniae and health outcomes in children with asthma

“…Real-time PCR for CARDS Tx (MPN372) was performed as described, 9,10 with the limit of detection (LOD) set at 5 genomes. CARDS Tx protein was quantified using AC as previously described 10 with LOD set at 0.078pg. Mp positive subjects were defined as those with any PCR or AC above the LOD, and Mp negative subjects were those in whom testing at a given visit was negative.…”

“…We developed assays to detect CARDS Tx by PCR and antigen capture (AC). 9,10 CARDS Tx gene sequences are more sensitive for the detection of Mp by PCR than other gene targets such as Mp P1 adhesin (P1) and adenosine triphosphatase. 11,12 …”

Functional mapping of community‐acquired respiratory distress syndrome (CARDS) toxin of Mycoplasma pneumoniae defines regions with ADP‐ribosyltransferase, vacuolating and receptor‐binding activities

“…In support of this idea, CARDS toxin expression is dramatically limited during mycoplasma growth in laboratory media, in contrast to its markedly up-regulated synthesis during M. pneumoniae infection of the airway (Kannan et al , 2010). CARDS toxin also elicits a strong immune response in convalescing humans and infected experimental animals and is readily detectable in airway fluids (Kannan et al, 2010, Techasaensiri et al , 2010, Kannan et al , 2011, Muir et al , 2011, Peters et al, 2011, Kannan et al , 2012). Furthermore, purified recombinant CARDS toxin elicits multiple inflammatory and temporally changing histopathological patterns in rodents and primates in a manner similar to those observed during M. pneumoniae infection (Hardy et al, 2009).…”

Mycoplasma pneumoniae in children with acute and refractory asthma

“…We have developed assays to detect CARDS Tx by PCR and antigen capture (AC) and to detect IgM and IgG antibodies directed against CARDS Tx (8–10) . CARDS Tx gene sequences are more sensitive for the detection of Mp by PCR than other sequences such as P1 adhesin (P1) and ATPase (11,12) .…”