Biochemical and immunological properties of lactoferrin binding proteins fromMoraxella (Branhamella) catarrhalis

Bonnah, Robert A.; Yu, Rong Hua; Wong, Henry Sung Ching; Schryvers, Anthony B.

doi:10.1006/mpat.1997.0173

Cited by 31 publications

(38 citation statements)

References 38 publications

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“…The human immune response to meningococcal LbpB has not been reported, but data from LbpB of M. catarrhalis indicate that patient sera elicit a strong immune response to the LbpB of this pathogen (25,139). Further, the TbpB homologue of LbpB is reported to elicit a strong bactericidal antibody response in humans.…”

Section: Downloaded Frommentioning

confidence: 99%

Iron Transport Systems in Neisseria meningitidis

Perkins-Balding

Ratliff-Griffin

Stojiljković

2004

Microbiol Mol Biol Rev

147

146

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SUMMARY Acquisition of iron and iron complexes has long been recognized as a major determinant in the pathogenesis of Neisseria meningitidis. In this review, high-affinity iron uptake systems, which allow meningococci to utilize the human host proteins transferrin, lactoferrin, hemoglobin, and haptoglobin-hemoglobin as sources of essential iron, are described. Classic features of bacterial iron transport systems, such as regulation by the iron-responsive repressor Fur and TonB-dependent transport activity, are discussed, as well as more specific features of meningococcal iron transport. Our current understanding of how N. meningitidis acquires iron from the human host and the vaccine potentials of various components of these iron transport systems are also reviewed.

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Section: Downloaded Frommentioning

confidence: 99%

Iron Transport Systems in Neisseria meningitidis

Perkins-Balding

Ratliff-Griffin

Stojiljković

2004

Microbiol Mol Biol Rev

147

146

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“…Several of these cell surface-exposed proteins have been characterized in some detail, including UspA1, UspA2 (HMWP), and UspA2H (24,26,32); OMP CD (21,34); the iron-regulated CopB protein (3,8); the LbpA and LbpB proteins (6); and the TbpA and TbpB proteins (7,28,35).…”

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confidence: 99%

Expression of the Moraxella catarrhalis UspA1 Protein Undergoes Phase Variation and Is Regulated at the Transcriptional Level

2001

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In the present study, cell lysates prepared from individual colonies of several M. catarrhalis wild-type strains were analyzed by Western blot analysis using monoclonal antibodies (MAbs) specific for the UspA1 protein. Expression of UspA1 was shown to exhibit phase variation that was correlated with both adherence ability in vitro and the number of guanine (G) residues contained within a homopolymeric [poly(G)]tract located upstream of the uspA1 open reading frame (ORF). Nucleotide sequence analysis revealed that isolates expressing relatively high levels of UspA1 had 10 G residues in their uspA1 poly(G)tracts, whereas isolates that expressed much lower levels of UspA1 had 9 G residues. This poly(G) tract was located 30 nucleotides (nt) upstream of the uspA1 ORF and 168 nt downstream of the uspA1 transcriptional start site. Primer extension experiments, RNA slot blot analysis, and cat reporter constructs were used to demonstrate that M. catarrhalis isolates with 10 G residues in their uspA1 poly(G) tracts expressed two-to threefold more uspA1 mRNA than did isolates which had 9 G residues in their poly(G)tracts. Northern hybridization analysis revealed that an intact uspA1 mRNA was readily detectable in RNA from M. catarrhalis isolates that had 10 G residues in their uspA1 poly(G) tracts, whereas no full-length uspA1 mRNA was observed in isolates whose poly(G)tracts contained 9 G residues. M. catarrhalis strain O35E uspA1 genes that contained wild-type and mutated poly(G) tracts were expressed in Haemophilus influenzae to demonstrate that the length and composition of the poly(G)tract affected expression of UspA1.Moraxella (Branhamella) catarrhalis is an unencapsulated gram-negative bacterium that can cause both upper and lower respiratory tract infections (14, 33). It has been estimated that M. catarrhalis causes approximately 20% of cases of acute bacterial otitis media in infants and young children (5) and is associated with nearly 30% of infectious exacerbations of chronic obstructive pulmonary disease in adults (17). The significant morbidity associated with M. catarrhalis infections as well as the substantial health care costs of these infections have prompted recent interest in the development of an M. catarrhalis vaccine (37).Proteins present in or closely associated with the outer membrane of M. catarrhalis strains obtained from diverse geographic and clinical sources display highly similar patterns when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) (4) and have received the most attention as potential vaccine candidates. Several of these cell surface-exposed proteins have been characterized in some detail, including UspA1, UspA2 (HMWP), and UspA2H (24,26,32); OMP CD (21, 34); the iron-regulated CopB protein (3, 8); the LbpA and LbpB proteins (6); and the TbpA and TbpB proteins (7,28,35).Little is known about the regulation of expression of M. catarrhalis outer membrane proteins. Campagnari et al. (8) were the first to show that the availability of iron in the growth ...

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“…The genes whose expression was most highly upregulated by iron limitation, as determined by DNA microarray analysis, included lbpB, lbpA, tbpB, copB, and several other genes predicted to encode proteins involved in iron uptake ( Table 3). The first four genes listed above have previously been shown to be up-regulated by iron limitation (3,12,14,43). The majority of the genes whose expression was most adversely affected by iron limitation encoded ribosomal proteins (Table 3); this is likely due to the growth inhibition caused by iron limitation (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…When total RNA extracted from M. catarrhalis cells grown under both iron-replete and iron-limiting conditions was subjected to DNA microarray analysis using probes derived from M. catarrhalis ATCC 43617, the genes that were markedly up-regulated included those previously shown by protein expression measurements (3,12,14,43) to be affected by the availability of iron in the growth environment. The DNA microarrays were then used to identify M. catarrhalis genes whose expression was affected by growth in a biofilm.…”

Section: Discussionmentioning

confidence: 99%

Metabolic Analysis of Moraxella catarrhalis and the Effect of Selected In Vitro Growth Conditions on Global Gene Expression

et al. 2007

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The nucleotide sequence from the genome of Moraxella catarrhalis ATCC 43617 was annotated and used both to assess the metabolic capabilities and limitations of this bacterium and to design probes for a DNA microarray. An absence of gene products for utilization of exogenous carbohydrates was noteworthy and could be correlated with published phenotypic data. Gene products necessary for aerobic energy generation were present, as were a few gene products generally ascribed to anaerobic systems. Enzymes for synthesis of all amino acids except proline and arginine were present. M. catarrhalis DNA microarrays containing 70-mer oligonucleotide probes were designed from the genome-derived nucleotide sequence data. Analysis of total RNA extracted from M. catarrhalis ATCC 43617 cells grown under iron-replete and iron-restricted conditions was used to establish the utility of these DNA microarrays. These DNA microarrays were then used to analyze total RNA from M. catarrhalis cells grown in a continuous-flow biofilm system and in the planktonic state. The genes whose expression was most dramatically increased by growth in the biofilm state included those encoding a nitrate reductase, a nitrite reductase, and a nitric oxide reductase. Real-time reverse transcriptase PCR analysis was used to validate these DNA microarray results. These results indicate that growth of M. catarrhalis in a biofilm results in increased expression of gene products which can function not only in energy generation but also in resisting certain elements of the innate immune response.Moraxella catarrhalis is a gram-negative, unencapsulated bacterium that can colonize the mucosal surface of the human nasopharynx, most frequently in infants and very young children (22). When this organism traverses the eustachian tube in these very young individuals, it can cause otitis media (7). Alternatively, in colonized adults, M. catarrhalis gains access to the bronchi and there causes exacerbations of chronic obstructive pulmonary disease (48). This organism can also infrequently cause other types of infections (for reviews, see references 39 and 73).Information about the virulence mechanisms employed by this organism in the production of disease is still very limited, although a number of putative virulence factors have been identified, including proteins located in or attached to the outer membrane (1, 6, 9, 23, 24, 26, 32-34, 40, 44, 49, 51, 54, 57, 65, 71), as well as lipooligosaccharide (42, 59). Validation of the actual involvement of these different gene products in disease processes has been severely hindered by the lack of an appropriate animal model for M. catarrhalis disease (39). Similarly, little is known about how M. catarrhalis colonizes the nasopharynx, and while several M. catarrhalis adhesins which function in vitro have been identified (33,40,61,71), the relative importance of these macromolecules in the colonization process in vivo remains to be determined. Recent studies aimed at addressing this issue have included the use of reverse transcr...

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Biochemical and immunological properties of lactoferrin binding proteins fromMoraxella (Branhamella) catarrhalis

Cited by 31 publications

References 38 publications

Iron Transport Systems in Neisseria meningitidis

Iron Transport Systems in Neisseria meningitidis

Expression of the Moraxella catarrhalis UspA1 Protein Undergoes Phase Variation and Is Regulated at the Transcriptional Level

Metabolic Analysis of Moraxella catarrhalis and the Effect of Selected In Vitro Growth Conditions on Global Gene Expression

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