Pneumococcal protein PavA is important for nasopharyngeal carriage and development of sepsis

Abstract

Summary The pneumococcal cell surface protein PavA is a virulence factor associated with adherence and invasion in vitro. In this study we show in vivo that PavA is necessary for Streptococcus pneumoniae D39 colonization of the murine upper respiratory tract in a long-term carriage model, with PavA-deficient pneumococci being quickly cleared from nasopharyngeal tissue. In a pneumonia model, pavA mutants were not cleared from the lungs of infected mice and persisted to cause chronic infection, whereas wild-type pneumococci caused systemic infection. Hence, under the experimental conditions, PavA-deficient pneumococci appeared to be unable to seed from lung tissue into blood, although they survived in blood when administered intravenously. In a meningitis model of infection, levels of PavA-deficient pneumococci in blood and brain following intercisternal injection were significantly lower than wild type. Taken collectively these results suggest that PavA is involved in successful colonization of mucosal surfaces and in translocation of pneumococci across host barriers. Pneumococcal sepsis is a major cause of mortality worldwide so identification of factors such as PavA that are necessary for carriage and for translocation from tissue to blood is of clinical and therapeutic importance.

Impact of Glutamine Transporters on Pneumococcal Fitness under Infection-Related Conditions

“…infection studies were performed with 6-to 8-week-old female CD-1 outbred mice (Charles River, Sulzfeld, Germany) as described recently (19,20,23). Bioluminescent pneumococci (23,25) were used to infect mice, which allows monitoring of bacterial dissemination in real time using the IVIS Lumina Imaging System (Xenogen Corporation, part of Caliper Life Sciences) as described previously (23,25).…”

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

“…In the in vivo infection experiments pneumococci-infected mice have to be monitored in intervals of 8-12 hr, since the spread of pneumococci can progress rapidly in outbred CD-1 mice. The real time imaging can be employed to visualize transmigration of pneumococci from the nasopharynx into the lung and blood, and in addition, the multiplication of pneumococci in the blood after intraperitoneal infection can be monitored by the dramatic increase in bioluminescence intensity 26,28,29 .…”

“…5. Use a pipette with long narrow tips (Gel Loader Tips) and drop bioluminescent pneumococci in multiple small droplets onto the nares (10 µl/ nostril) of the mouse [26][27][28][29] . The mouse will involuntarily inhale the bacteria.…”

“…In pneumococci the optimized luxABCDE gene cassette (plasmid pAUL-A Tn4001 luxABCDE Km r ) has been inserted into a single integration site of the chromosome by transposon mutagenesis. Bioluminescent pneumococci have been employed to assess the attenuation of pneumococcal mutants deficient in virulence or fitness factors and their translocation from one anatomical site to another 26,[28][29][30][31] .…”

Review: Current and new generation pneumococcal vaccines

“…[91][92][93][94][95][96][97] In addition, PavB and PfbA, as well as PavA, promote the attachment of the pneumococcus to fibronectin, a component of the extracellular matrix.…”