Infant rat infection modifies phenotypic properties of an invasive nontypeable Haemophilus influenzae.
Enhancing the virulence trait of a specific bacterium in an animal model is often performed prior to the use of the strain for ex vivo human studies, such as reactivity with complement and antibody, or with phagocytic cells. For example, in Streptococcus pneumoniae mouse passage is used to enhance capsule production. While investigating an unusual serum-resistant unencapsulated Haemophilus influenzae (R2866), we found that animal passage yielded an isolate (R3392) which had decreased resistance to human serum, but increased virulence in Chang conjunctival cell monolayers, but with less invasion and transcytosis of polar H292 cells. We examined 90 colonies recovered from three infant rats for phase variants of LPS biosynthetic genes. In 88 colonies lgtC was OFF due to tetrameric repeat mediated slipped-strand mispairing at the time of DNA replication, while there was no variation in lic1A, lic2A, lic3A, lexA and oaf A. With lgtC OFF the LPS lacks Galα1-4βGal, an epitope mimicking the human p(k) blood group, and molecular mimicry is lost. Selection for strain susceptible to NHS in the infant rat was not antibody mediated. We conclude that the passage of pathogens virulent in humans and animals may select for phenotypes only relevant for the animal species used.
Rinat Laboratories, Biotherapeutics Division, Pfizer, San Francisco, CA 94080, USA.
David
D
Tsao
Kevin L
KL
Nelson
Daniel
D
Kim
Arnold L
AL
Smith
D000328:Adult; D000818:Animals; D000831:Animals, Newborn; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001770:Blood Bactericidal Activity; D002460:Cell Line; D003228:Conjunctiva / Q000382:microbiology; D005260:Female; D006192:Haemophilus Infections / Q000382:microbiology*; D006193:Haemophilus influenzae / Q000145:classification* / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D020128:Inhibitory Concentration 50; D008070:Lipopolysaccharides / Q000096:biosynthesis; D050296:Microbial Viability; D010641:Phenotype; D011247:Pregnancy; D051381:Rats; D012692:Serial Passage; D014774:Virulence
D001426:Bacterial Proteins; D008070:Lipopolysaccharides