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Following in Real Time the Impact of Pneumococcal Virulence Factors in an Acute Mouse Pneumonia Model Using Bioluminescent Bacteria

Following in Real Time the Impact of Pneumococcal Virulence Factors in an Acute Mouse Pneumonia Model Using Bioluminescent Bacteria

Published on: February 23, 2014

A pneumolysin-negative mutant of Streptococcus pneumoniae causes chronic bacteremia rather than acute sepsis in mice

K A Benton¹, M P Everson, D E Briles

¹Department of Microbiology, University of Alabama at Birmingham.

Infection and Immunity

|February 1, 1995

Abstract:

Pneumolysin is a cytoplasmic virulence factor of Streptococcus pneumoniae that can interfere with phagocyte function in vitro. We have examined the effects of pneumolysin in vitro and in vivo and have found that it protects intravenously injected pneumococci against infection-induced host resistance. We employed a virulent capsular type 2 pneumococcal strain, D39, and its isogenic pneumolysin-negative mutant, PLN. Strain D39 exhibited exponential net growth in mice (doubling time, 1.4 h); 24 to 28 h after infection with 10(4) CFU, the numbers of pneumococci reached 10(9) to 10(10) CFU/ml and the mice died. Strain PLN yielded identical net growth in mice until reaching 10(6) to 10(7) CFU/ml at 12 to 18 h postinfection. At this time, the increase in the level of PLN CFU per milliliter ceased and remained constant for several days. PLN exhibited wild-type growth kinetics in mice when coinfected simultaneously with strain D39. This observation suggests that pneumolysin exerts its effects at a distance. By 12 to 18 h postinfection with PLN, mice exhibited the following evidence of an induced inflammatory response: (i) elevated plasma interleukin-6, (ii) a halt in the net growth of PLN, and (iii) control of the net growth of pneumolysin-producing D39 pneumococci upon subsequent challenge. Our data suggest that pneumolysin plays a critical role in sepsis during the first few hours after infection by enabling pneumococci to cause acute sepsis rather than a chronic bacteremia. However, once chronic bacteremia was established, it appeared that pneumolysin was no longer able to act as a virulence factor.

Insights

Pneumolysin, a Streptococcus pneumoniae virulence factor, protects bacteria from host resistance during early sepsis. It enables acute sepsis by preventing an effective immune response, but its role diminishes as infection progresses.

Area of Science:

Microbiology
Immunology
Infectious Diseases

Background:

Pneumolysin is a key virulence factor of Streptococcus pneumoniae.
It is known to interfere with phagocyte function in vitro.
Its role in vivo during pneumococcal infections remains to be fully elucidated.

Purpose of the Study:

To investigate the role of pneumolysin in Streptococcus pneumoniae infections in vivo.
To determine how pneumolysin affects host resistance and bacterial growth during sepsis.
To understand the temporal activity of pneumolysin as a virulence factor.

Main Methods:

Comparison of a virulent Streptococcus pneumoniae strain (D39) and its isogenic pneumolysin-negative mutant (PLN) in a murine model.
Monitoring bacterial growth kinetics (CFU/ml) and host inflammatory markers (interleukin-6) over time.
Assessing the impact of pneumolysin on host resistance and bacterial dissemination.

Main Results:

Pneumolysin-producing D39 exhibited exponential growth and rapid mortality in mice.
The pneumolysin-negative PLN mutant showed transient growth followed by a halt, correlating with an induced inflammatory response.
Coinfection with D39 restored wild-type growth kinetics to PLN, indicating pneumolysin acts at a distance.
Elevated interleukin-6 levels were observed in mice infected with PLN, suggesting an early immune response.

Conclusions:

Pneumolysin is crucial for Streptococcus pneumoniae to establish acute sepsis by evading early host resistance.
The virulence factor enables rapid bacterial proliferation in the initial hours of infection.
Pneumolysin's protective effect against host resistance is most significant during the early stages of infection, diminishing as chronic bacteremia develops.

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