HOW PNEUMONIA BACTERIA CAN COMPROMISE HEART HEALTH
Bacterial pneumonia in
adults carries an elevated risk for adverse cardiac events (such as heart
failure, arrhythmias, and heart attacks) that contribute substantially to
mortality -- but how the heart is compromised has been unclear. A study
published on September 18th in PLOS Pathogens now demonstrates that Streptococcus
pneumoniae, the bacterium
responsible for most cases of bacterial pneumonia, can invade the heart and
cause the death of heart muscle cells.
Carlos Orihuela, from
the University of Texas Health Science Center in San Antonio, USA, and
colleagues initially studied the reasons for heart failure during invasive
pneumococcal disease (when S. pneumoniaebacteria infect major
organs such as the lungs, bloodstream, and brain) in mice, and subsequently
confirmed some of their main findings in rhesus macaques and in heart tissue
from deceased human patients.
Mice with severe
invasive pneumococcal disease showed elevated levels of troponin, a marker for
heart injury, in their blood. They also had abnormal EKGs. When the researchers
examined the hearts of the mice, they found microscopic sites of injury (called
microlesions) in the heart muscle. S. pneumoniaewere found within
these microlesions, indicating the bacteria were able to invade and multiply
within the heart. Looking in more detail, the researchers identified dying
heart muscle cells in the tissue surrounding microlesions.
At the molecular
level, the researchers found that the S. pneumoniae toxin
pneumolysin was present within the microlesions and responsible for heart
muscle cell death. They also showed that S. pneumoniae requires
a molecule called CbpA to exit the bloodstream and invade the heart. Moreover,
an experimental vaccine formulation composed of CbpA and a non-toxic version of
pneumolysin generated antibodies that protected mice against cardiac invasion
and heart damage.
Having obtained
tissues from three rhesus macaques that had died from pneumococcal pneumonia,
the researchers found cardiac microlesions that were similar in size and
appearance to those seen in mice, but without the presence of S.
pneumoniae bacteria. The situation was similar in cardiac samples from
human patients who had died from invasive pneumococcal disease. Two of the
samples (they looked at a total of nine) showed microlesions, but the lesions
did not contain bacteria.
As the macaques and
the human patients had been treated with antibiotics, the researchers wondered
whether the bacteria had caused the lesions but subsequently been killed by the
treatment. To test this, they infected mice with S. pneumoniae and
treated them with a high-dose antibiotic (ampicillin) when the lesions were
first apparent. The hearts of these mice looked similar to the macaques and
human samples, with clear presence of microlesions but devoid of bacteria. As
the researchers discuss, ampicillin acts by breaking bacteria apart and
releasing their contents, including pneumolysin, and this could exacerbate the
death of heart muscle cells. Alternative antibiotics that do not spill their
bacterial targets' contents exist and might be advantageous.
Having shown for the
first time that S. pneumoniae can directly damage the heart --
which could help explain the link between pneumonia and adverse heart events --
the researchers conclude that "research is merited to determine the true
frequency of cardiac microlesions in patients hospitalized with invasive pneumococcal
disease, if modifications in antibiotic therapy improve long-term outcomes, and
if prevention of cardiac damage is an indication for vaccination."
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