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 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.
Molecular Bacteriology and Immunology Group, School of Molecular Medical Sciences, University of Nottingham, Nottingham, United Kingdom.
Neil J
NJ
Oldfield
Suzan
S
Matar
Fadil A
FA
Bidmos
Mohammed
M
Alamro
Keith R
KR
Neal
David P J
DP
Turner
Christopher D
CD
Bayliss
Dlawer A A
DA
Ala'aldeen
D002353:Carrier State; D015964:Gene Expression Regulation, Bacterial; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D008589:Meningococcal Infections / Q000382:microbiology*; D009345:Neisseria meningitidis / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism / Q000472:pathogenicity*; D010641:Phenotype; D011066:Poly C / Q000235:genetics; D018272:Porins / Q000235:genetics* / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D012703:Serotyping; D014774:Virulence
D026901:Membrane Transport Proteins; D018272:Porins; D011066:Poly C; C480853:NalP protein, Neisseria meningitidis; D012697:Serine Endopeptidases