title: Haemophilus influenzae LicB contributes to lung damage in an aged mice co-infection model.
abstract: Phosphorylcholine (ChoP) decoration of lipopolysaccharides is an important virulence strategy adopted by Haemophilus influenzae to establish a niche on the mucosal surface and to promote adherence to the host cells. The incorporation of ChoP on the LPS surface involves the lic1 operon, which consists of the licA, licB, licC, and licD genes. Among which, licB is a choline transporter gene required for acquisition of choline from environmental sources. In this study, we investigated the pathogenesis of the licB gene in an aged mice infection model. Due to immediate clearance of H. influenzae upon infection in mice, we employed influenza A virus and H. influenzae co-infection model. Our data showed that in the co-infection model, the secondary bacterial infection with a very low H. influenzae concentration of 100 colony forming unit is lethal to the aged mice. Although we did not observe any differences in weight loss between parent and licB mutant strains during the course of infection, a significant reduction of lung tissue damage was observed in the licB mutant infected aged mice. These results suggest that the licB gene is a virulence factor during H. influenzae infection in the lung in aged mice, possibly due to the increased binding to the host cell receptor via ChoP expression on the bacterial surface. In addition, when aged mice and mature mice were compared in the challenge experiments, we did not observe any protective immunity in the co-infection model suggesting the detrimental effects of the secondary bacterial infection on the aged mice in contrast to obvious immune-protections observed in the mature mice. The results of our experiments also implied that the co-infection model with influenza A virus and H. influenzae may be employed as a model system to study H. influenzae pathogenesis in vivo in aged mice.
authors.affiliation: West Chester University of Pennsylvania, Department of Biology, 750 South Church Street, West Chester, PA 19383, USA. Electronic address: JB740149@wcupa.edu.
authors.forename: Jessica
authors.initials: J
authors.lastname: Bondy
authors.affiliation: West Chester University of Pennsylvania, Department of Biology, 750 South Church Street, West Chester, PA 19383, USA. Electronic address: sofyaosharo@gmail.com.
authors.forename: Sofya
authors.initials: S
authors.lastname: Osharovich
authors.affiliation: West Chester University of Pennsylvania, Department of Biology, 750 South Church Street, West Chester, PA 19383, USA. Electronic address: j.storm309@gmail.com.
authors.forename: Julie
authors.initials: J
authors.lastname: Storm
authors.affiliation: West Chester University of Pennsylvania, Department of Biology, 750 South Church Street, West Chester, PA 19383, USA. Electronic address: gdurning12@gmail.com.
authors.forename: Graham
authors.initials: G
authors.lastname: Durning
authors.affiliation: University of Pennsylvania, School of Arts and Sciences, 433 S University Ave., Philadelphia, PA 19104, USA. Electronic address: tmcau@sas.upenn.edu.
authors.forename: Timothy
authors.initials: T
authors.lastname: McAuliffe
authors.affiliation: West Chester University of Pennsylvania, Department of Biology, 750 South Church Street, West Chester, PA 19383, USA. Electronic address: xfan@wcupa.edu.
authors.forename: Xin
authors.initials: X
authors.lastname: Fan
mesh_terms: D000367:Age Factors; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D060085:Coinfection / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology / Q000821:virology; D004195:Disease Models, Animal; D006192:Haemophilus Infections / Q000378:metabolism / Q000382:microbiology* / Q000821:virology; D006193:Haemophilus influenzae / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D009980:Influenza A virus / Q000235:genetics / Q000302:isolation & purification* / Q000472:pathogenicity; D008070:Lipopolysaccharides / Q000378:metabolism; D008168:Lung / Q000382:microbiology / Q000473:pathology* / Q000821:virology; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009154:Mutation; D009976:Orthomyxoviridae Infections / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology / Q000821:virology; D010767:Phosphorylcholine / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000378:metabolism; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; C497250:Ddit3 protein, mouse; D008070:Lipopolysaccharides; D026901:Membrane Transport Proteins; C065637:choline transporter; D010767:Phosphorylcholine; D051742:Transcription Factor CHOP; D002794:Choline
keywords: Aged mice; Co-infection; Immunoprotection; Lung pathogenesis; Phosphorylcholine