title: The effects of differences in pspA alleles and capsular types on the resistance of Streptococcus pneumoniae to killing by apolactoferrin.
abstract: Pneumococcal surface protein A (PspA) is the only pneumococcal surface protein known to strongly bind lactoferrin on the bacterial surface. In the absence of PspA Streptococcus pneumoniae becomes more susceptible to killing by human apolactoferrin (apo-hLf), the iron-free form of lactoferrin. In the present study we examined diverse strains of S. pneumoniae that differed by 2 logs in their susceptibility to apo-hLf. Among these strains, the amount of apo-hLf that bound to cell surface PspA correlated directly with the resistance of the strain to killing by apo-hLf. Moreover examination of different pspA alleles on shared genetic backgrounds revealed that those PspAs that bound more lactoferrin conferred greater resistance to killing by apo-hLf. The effects of capsule on killing of pneumococci by apo-hLf were generally small, but on one genetic background, however, the lack of capsule was associated with 4-times as much apo-hLf binding and 30-times more resistance to killing by apo-hLf. Overall these finding strongly support the hypothesis that most of the variation in the ability of apo-hLf is dependent on the variation in the binding of apo-hLf to surface PspA and this binding is dependent on variation in PspA as well as variation in capsule which may enhance killing by reducing the binding of apo-hLf to PspA.
authors: Department of Biology, Lahore University of Management Sciences, Pakistan; Division of Epidemiology, Human Genetics and Environmental Health, School of Public Health, University of Texas, Health Science Center, Brownsville Regional Campus, TX, USA. Electronic address: Shaper.Mirza@lums.edu.pk.
authors: Shaper
authors: S
authors: Mirza
authors: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA; Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
authors: William H
authors: WH
authors: Benjamin
authors: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
authors: Patricia A
authors: PA
authors: Coan
authors: Department of Pathology and Laboratory Medicine, Medical School University of Texas Health Science Center, Houston, TX, USA.
authors: Shen-An
authors: SA
authors: Hwang
authors: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
authors: Anne-Kathryn
authors: AK
authors: Winslett
authors: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
authors: Janet
authors: J
authors: Yother
authors: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
authors: Susan K
authors: SK
authors: Hollingshead
authors: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA; Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA; Department of Pediatrics Dentistry, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
authors: Kohtaro
authors: K
authors: Fujihashi
authors: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA; Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
authors: David E
authors: DE
authors: Briles
mesh_terms: D000483:Alleles; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D001059:Apoproteins / Q000378:metabolism*; D016667:Bacterial Capsules / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D014644:Genetic Variation; D006801:Humans; D007781:Lactoferrin / Q000378:metabolism*; D050296:Microbial Viability / Q000187:drug effects*; D011485:Protein Binding; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001059:Apoproteins; D001426:Bacterial Proteins; C039223:apolactoferrin; C051592:pneumococcal surface protein A; D007781:Lactoferrin