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Prevalence and Phase Variable Expression Status of Two Autotransporters, NalP and MspA, in Carriage and Disease Isolates of Neisseria meningitidis

Neisseria meningitidis is a human nasopharyngeal commensal capable of causing life-threatening septicemia and meningitis. Many meningococcal surface structures, including the autotransporter proteins NalP and MspA, are subject to phase variation (PV) due to the presence of homopolymeric tracts withi...

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Autores principales: Oldfield, Neil J., Matar, Suzan, Bidmos, Fadil A., Alamro, Mohammed, Neal, Keith R., Turner, David P. J., Bayliss, Christopher D., Ala’Aldeen, Dlawer A. A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3723659/
https://www.ncbi.nlm.nih.gov/pubmed/23936091
http://dx.doi.org/10.1371/journal.pone.0069746
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author Oldfield, Neil J.
Matar, Suzan
Bidmos, Fadil A.
Alamro, Mohammed
Neal, Keith R.
Turner, David P. J.
Bayliss, Christopher D.
Ala’Aldeen, Dlawer A. A.
author_facet Oldfield, Neil J.
Matar, Suzan
Bidmos, Fadil A.
Alamro, Mohammed
Neal, Keith R.
Turner, David P. J.
Bayliss, Christopher D.
Ala’Aldeen, Dlawer A. A.
author_sort Oldfield, Neil J.
collection PubMed
description Neisseria meningitidis is a human nasopharyngeal commensal capable of causing life-threatening septicemia and meningitis. Many meningococcal surface structures, including the autotransporter proteins NalP and MspA, are subject to phase variation (PV) due to the presence of homopolymeric tracts within their coding sequences. The functions of MspA are unknown. NalP proteolytically cleaves several surface-located virulence factors including the 4CMenB antigen NhbA. Therefore, NalP is a phase-variable regulator of the meningococcal outer membrane and secretome whose expression may reduce isolate susceptibility to 4CMenB-induced immune responses. To improve our understanding of the contributions of MspA and NalP to meningococcal-host interactions, their distribution and phase-variable expression status was studied in epidemiologically relevant samples, including 127 carriage and 514 invasive isolates representative of multiple clonal complexes and serogroups. Prevalence estimates of >98% and >88% were obtained for mspA and nalP, respectively, with no significant differences in their frequencies in disease versus carriage isolates. 16% of serogroup B (MenB) invasive isolates, predominately from clonal complexes ST-269 and ST-461, lacked nalP. Deletion of nalP often resulted from recombination events between flanking repetitive elements. PolyC tract lengths ranged from 6–15 bp in nalP and 6–14 bp in mspA. In an examination of PV status, 58.8% of carriage, and 40.1% of invasive nalP-positive MenB isolates were nalP phase ON. The frequency of this phenotype was not significantly different in serogroup Y (MenY) carriage strains, but was significantly higher in invasive MenY strains (86.3%; p<0.0001). Approximately 90% of MenB carriage and invasive isolates were mspA phase ON; significantly more than MenY carriage (32.7%) or invasive (13.7%) isolates. This differential expression resulted from different mode mspA tract lengths between the serogroups. Our data indicates a differential requirement for NalP and MspA expression in MenB and MenY strains and is a step towards understanding the contributions of phase-variable loci to meningococcal biology.
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spelling pubmed-37236592013-08-09 Prevalence and Phase Variable Expression Status of Two Autotransporters, NalP and MspA, in Carriage and Disease Isolates of Neisseria meningitidis Oldfield, Neil J. Matar, Suzan Bidmos, Fadil A. Alamro, Mohammed Neal, Keith R. Turner, David P. J. Bayliss, Christopher D. Ala’Aldeen, Dlawer A. A. PLoS One Research Article Neisseria meningitidis is a human nasopharyngeal commensal capable of causing life-threatening septicemia and meningitis. Many meningococcal surface structures, including the autotransporter proteins NalP and MspA, are subject to phase variation (PV) due to the presence of homopolymeric tracts within their coding sequences. The functions of MspA are unknown. NalP proteolytically cleaves several surface-located virulence factors including the 4CMenB antigen NhbA. Therefore, NalP is a phase-variable regulator of the meningococcal outer membrane and secretome whose expression may reduce isolate susceptibility to 4CMenB-induced immune responses. To improve our understanding of the contributions of MspA and NalP to meningococcal-host interactions, their distribution and phase-variable expression status was studied in epidemiologically relevant samples, including 127 carriage and 514 invasive isolates representative of multiple clonal complexes and serogroups. Prevalence estimates of >98% and >88% were obtained for mspA and nalP, respectively, with no significant differences in their frequencies in disease versus carriage isolates. 16% of serogroup B (MenB) invasive isolates, predominately from clonal complexes ST-269 and ST-461, lacked nalP. Deletion of nalP often resulted from recombination events between flanking repetitive elements. PolyC tract lengths ranged from 6–15 bp in nalP and 6–14 bp in mspA. In an examination of PV status, 58.8% of carriage, and 40.1% of invasive nalP-positive MenB isolates were nalP phase ON. The frequency of this phenotype was not significantly different in serogroup Y (MenY) carriage strains, but was significantly higher in invasive MenY strains (86.3%; p<0.0001). Approximately 90% of MenB carriage and invasive isolates were mspA phase ON; significantly more than MenY carriage (32.7%) or invasive (13.7%) isolates. This differential expression resulted from different mode mspA tract lengths between the serogroups. Our data indicates a differential requirement for NalP and MspA expression in MenB and MenY strains and is a step towards understanding the contributions of phase-variable loci to meningococcal biology. Public Library of Science 2013-07-25 /pmc/articles/PMC3723659/ /pubmed/23936091 http://dx.doi.org/10.1371/journal.pone.0069746 Text en © 2013 Oldfield et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Oldfield, Neil J.
Matar, Suzan
Bidmos, Fadil A.
Alamro, Mohammed
Neal, Keith R.
Turner, David P. J.
Bayliss, Christopher D.
Ala’Aldeen, Dlawer A. A.
Prevalence and Phase Variable Expression Status of Two Autotransporters, NalP and MspA, in Carriage and Disease Isolates of Neisseria meningitidis
title Prevalence and Phase Variable Expression Status of Two Autotransporters, NalP and MspA, in Carriage and Disease Isolates of Neisseria meningitidis
title_full Prevalence and Phase Variable Expression Status of Two Autotransporters, NalP and MspA, in Carriage and Disease Isolates of Neisseria meningitidis
title_fullStr Prevalence and Phase Variable Expression Status of Two Autotransporters, NalP and MspA, in Carriage and Disease Isolates of Neisseria meningitidis
title_full_unstemmed Prevalence and Phase Variable Expression Status of Two Autotransporters, NalP and MspA, in Carriage and Disease Isolates of Neisseria meningitidis
title_short Prevalence and Phase Variable Expression Status of Two Autotransporters, NalP and MspA, in Carriage and Disease Isolates of Neisseria meningitidis
title_sort prevalence and phase variable expression status of two autotransporters, nalp and mspa, in carriage and disease isolates of neisseria meningitidis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3723659/
https://www.ncbi.nlm.nih.gov/pubmed/23936091
http://dx.doi.org/10.1371/journal.pone.0069746
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