Modeling Neisseria meningitidis Infection in Mice: Methods and Logistical Considerations for Nasal Colonization and Invasive Disease

Abstract Background. Healthcare-associated infections pose a potentially fatal threat to patients worldwide and Staphylococcus aureus is one of the most common causes of healthcare-associated infections. S. aureus is a common commensal pathogen and a frequent cause of bacteremia, with studies demonstrating that nasal and blood isolates from single patients match more than 80% of the time. Here we report on a contemporary collection of colonizing isolates from those with methicillin-resistant S. aureus (MRSA) bloodstream infections to evaluate the diversity within hosts, and detail the clinical features associated with concomitant nasal colonization.Methods. Swabs of the bilateral anterior nares were obtained from patients diagnosed with MRSA bacteremia. A single colony culture from the blood and an average of 6 colonies from the nares were evaluated for MRSA growth. For the nares cultures, we typed multiple isolates for staphylococcal protein A (spa) and derived the clonal complexes. Demographic and clinical data were obtained retrospectively from the electronic medical record system and analysed using univariate and multivariable regression models.Results. Over an 11-month period, 68 patients were diagnosed with MRSA bloodstream infection, 53 were swabbed, and 37 (70%) were colonized with MRSA in the anterior nares. We performed molecular typing on 210 nasal colonies. Spa types and clonal complexes found in the blood were also detected in the nares in 95% of the cases. We also found that 11% of patients carried more than one clone of MRSA in the nares. Male sex and history of prior hospitalization within the past 90 days increased odds for MRSA colonization. Conclusion. The molecular epidemiological landscape of colonization in the setting of invasive disease is diverse and defining the interplay between colonization and invasive disease is critical to combating invasive MRSA disease.

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Functional diversity of three different DsbA proteins from Neisseria meningitidis

Microbiology ◽

10.1099/mic.0.27216-0 ◽

2004 ◽

Vol 150 (9) ◽

pp. 2993-3000 ◽

Cited By ~ 32

Author(s):

Sunita Sinha ◽

Paul R. Langford ◽

J. Simon Kroll

Keyword(s):

Escherichia Coli ◽

Alkaline Phosphatase ◽

Protein Folding ◽

Membrane Proteins ◽

Neisseria Meningitidis ◽

Outer Membrane Proteins ◽

Invasive Disease ◽

Neisseria Lactamica ◽

Neisseria Subflava ◽

Neisseria Flavescens

The genome of Neisseria meningitidis serogroup B strain MC58 contains three genes – nmb0278, nmb0294 and nmb0407 – encoding putative homologues of DsbA, a periplasmic thiol disulphide oxidoreductase protein-folding catalyst of the Dsb protein family. DsbA assists the folding of periplasmic and membrane proteins in diverse organisms. While all three cloned genes complemented the DTT sensitivity of dsbA-null Escherichia coli, they showed different activities in folding specific target proteins in this background. NMB0278 protein was the most active in complementing defects in motility and alkaline phosphatase activity, while NMB0294 was the most active in folding periplasmic MalF. NMB0407 showed the weakest activity in all assays. It is extremely unusual for organisms to contain more than one chromosomal dsbA. Among the members of the genus Neisseria, only the meningococcus carries all three of these genes. Strains of Neisseria gonorrhoeae, Neisseria lactamica, Neisseria cinerea and Neisseria polysaccharea contained only homologues of nmb0278 and nmb0407, while Neisseria flava, Neisseria subflava and Neisseria flavescens carried only nmb0294. It is speculated that the versatility of the meningococcus in surviving in different colonizing and invasive disease settings may be derived in part from an enhanced potential to deploy outer-membrane proteins, a consequence of carrying an extended repertoire of protein-folding catalysts.

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Transmission Dynamics and Microevolution of Neisseria meningitidis During Carriage and Invasive Disease in High School Students in Georgia and Maryland, 2006–2007

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa674 ◽

2020 ◽

Author(s):

Mustapha M Mustapha ◽

Jane W Marsh ◽

Kathleen A Shutt ◽

Jessica Schlackman ◽

Chinelo Ezeonwuka ◽

...

Keyword(s):

High School ◽

High School Students ◽

Neisseria Meningitidis ◽

Allelic Variation ◽

Invasive Disease ◽

Geographic Region ◽

School Students ◽

Single Strain ◽

Bacterial Surface ◽

Culture Positive

Abstract Background The mechanisms by which Neisseria meningitidis cause persistent human carriage and transition from carriage to invasive disease have not been fully elucidated. Methods Georgia and Maryland high school students were sampled for pharyngeal carriage of N. meningitidis during the 2006–2007 school year. A total of 321 isolates from 188 carriers and all 67 invasive disease isolates collected during the same time and from the same geographic region underwent whole-genome sequencing. Core-genome multilocus sequence typing was used to compare allelic profiles, and direct read mapping was used to study strain evolution. Results Among 188 N. meningitidis culture–positive students, 98 (52.1%) were N. meningitidis culture positive at 2 or 3 samplings. Most students who were positive at >1 sampling (98%) had persistence of a single strain. More than a third of students carried isolates that were highly genetically related to isolates from other students in the same school, and occasional transmission within the same county was also evident. The major pilin subunit gene, pilE, was the most variable gene, and no carrier had identical pilE sequences at different time points. Conclusion We found strong evidence of local meningococcal transmission at both the school and county levels. Allelic variation within genes encoding bacterial surface structures, particularly pilE, was common.

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Neisseria meningitidis Intermediately Resistant to Penicillin and Causing Invasive Disease in South Africa in 2001 to 2005

Journal of Clinical Microbiology ◽

10.1128/jcm.00221-08 ◽

2008 ◽

Vol 46 (10) ◽

pp. 3208-3214 ◽

Cited By ~ 20

Author(s):

M. du Plessis ◽

A. von Gottberg ◽

C. Cohen ◽

L. de Gouveia ◽

K. P. Klugman ◽

...

Keyword(s):

South Africa ◽

Neisseria Meningitidis ◽

Invasive Disease

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Discordant Effects of Licensed Meningococcal Serogroup B Vaccination on Invasive Disease and Nasal Colonization in a Humanized Mouse Model

The Journal of Infectious Diseases ◽

10.1093/infdis/jix162 ◽

2017 ◽

Vol 215 (10) ◽

pp. 1590-1598 ◽

Cited By ~ 6

Author(s):

Carolyn M. Buckwalter ◽

Elissa G. Currie ◽

Raymond S. W. Tsang ◽

Scott D. Gray-Owen

Keyword(s):

Mouse Model ◽

Invasive Disease ◽

Nasal Colonization ◽

Humanized Mouse ◽

Humanized Mouse Model

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Surveillance of invasive meningococcal disease in the Czech Republic

Eurosurveillance ◽

10.2807/esm.09.11.00488-en ◽

2004 ◽

Vol 9 (11) ◽

pp. 11-12 ◽

Cited By ~ 5

Author(s):

P Kriz

Keyword(s):

Czech Republic ◽

Neisseria Meningitidis ◽

Meningococcal Disease ◽

Western Europe ◽

Vaccination Strategy ◽

Invasive Disease ◽

Invasive Meningococcal Disease ◽

Mortality Data ◽

Meningococcal Infections ◽

The Czech Republic

Routine notification of invasive meningococcal disease has a long tradition in the Czech Republic: mortality data are available from 1921 and morbidity data from 1943. The collection of Neisseria meningitidis strains kept in the NRL for Meningococcal Infections in Prague dates from 1970 onwards, and represents more than 3500 strains isolated from invasive disease and their contacts, from healthy carriers and from respiratory infection. Analysis of these strains showed that the Czech meningococcal population is different from that seen in western Europe. In 1993, the incidence serogroup C meningococcal disease increased and was associated with the emergence of the hypervirulent complex Neisseria meningitidis C, ST-11, ET-15/37, and caused an increase in the incidence of invasive meningococcal disease which peaked in 1995 (2.2/100 000). A vaccination strategy targeting the part of the population at highest risk of invasive meningococcal disease was adopted in the country.

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The spread of chloramphenicol-resistant Neisseria meningitidis in Southeast Asia

10.1101/2019.12.13.872499 ◽

2019 ◽

Author(s):

Elizabeth M. Batty ◽

Tomas-Paul Cusack ◽

Janjira Thaipadungpanit ◽

Wanitda Watthanaworawit ◽

Verena Carrara ◽

...

Keyword(s):

Southeast Asia ◽

Neisseria Meningitidis ◽

Democratic Republic ◽

Invasive Disease ◽

Health Concern ◽

Chloramphenicol Resistance ◽

Ciprofloxacin Resistance ◽

Diagnostic Microbiology ◽

Susceptibility Patterns ◽

Significant Health

AbstractInvasive disease caused by Neisseria meningitidis is a significant health concern globally, but our knowledge of the prevailing serogroups, antimicrobial susceptibility patterns, and genetics of N. meningitidis in Southeast Asia is limited. Chloramphenicol resistance in N. meningitidis has rarely been reported, but was first described in isolates from Vietnam in 1998. Using whole-genome sequencing of meningococcal isolates from 18 patients collected between 2007 and 2018 from diagnostic microbiology laboratories in Cambodia, Thailand and the Lao People’s Democratic Republic (Laos), of which eight were non-susceptible to chloramphenicol, we report the spread of this chloramphenicol-resistant lineage of N. meningitidis across Southeast Asia. Strains resistant to penicillin, tetracycline, and ciprofloxacin were also observed, including a chloramphenicol-resistant strain from the previously-described lineage which has acquired penicillin and ciprofloxacin resistance, and most isolates were of serogroup B. This study suggests that chloramphenicol-resistant N. meningitidis is more widespread than previously thought.

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Prevention of Neisseria meningitidis

Pediatrics in Review ◽

10.1542/pir.13.10.370 ◽

1992 ◽

Vol 13 (10) ◽

pp. 370-399

Keyword(s):

United States ◽

Neisseria Meningitidis ◽

Sporadic Case ◽

The United States ◽

Invasive Disease ◽

High Rate ◽

Meningococcal Infection ◽

Primary Case ◽

Household Members ◽

Spread Of Infection

Neisseria meningitidis causes approximately 3000 cases of invasive disease annually in the United States. A high rate of nasopharyngeal carriage occurs in household contacts of persons with invasive disease. During an epidemic (a situation that is more common outside of the United States), secondary attack rates in family members may be as high as 4% to 5%. Following a sporadic case of meningococcal disease, the secondary attack rate is approximately 3 per 1000 household members. Chemoprophylaxis has been very effective in preventing secondary spread of infection, especially if used within 24 h of diagnosing a primary case. Groups that become carriers and should receive chemoprophylaxis are the most likely to have had contact with the oral secretions of a case of invasive meningococcal infection.

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Neisseria meningitidis Bacteremia in Children: Quantitation of Bacteremia and Spontaneous Clinical Recovery Without Antibiotic Therapy

PEDIATRICS ◽

10.1542/peds.80.1.63 ◽

1987 ◽

Vol 80 (1) ◽

pp. 63-67 ◽

Cited By ~ 1

Author(s):

T. Dennis Sullivan ◽

Leonard J. LaScolea

Keyword(s):

Blood Culture ◽

Antibiotic Therapy ◽

Neisseria Meningitidis ◽

Invasive Disease ◽

Blood Cultures ◽

Negative Blood Culture ◽

Clinical Recovery ◽

Oral Amoxicillin ◽

Occult Bacteremia ◽

The Relationship

The relationship between the magnitude of bacteremia due to Neisseria meningitidis and the clinical diagnosis was determined for 43 children who had fever in the presence or absence of focal signs of infection. Bacteremia was quantitated by the previously described procedure using heparinized blood (0.2 to 1.0 mL). Additionally, blood was cultured by means of the radiometric Bactec technique. Seventeen patients had meningitis, 12 had meningococcemia, 13 had unsuspected or "occult" bacteremia, and five had other diagnoses. "Occult" bactermia was diagnosed initially in four patients, but subsequently meningitis was diagnosed. All 13 patients with 500 or more organisms per milliliter had meningitis or meningococcemia in contrast to 12 (55%) of 22 patients with less than 500 organisms per milliliter (P ≤ .0035). Only 18 (42%) of these patients bacteremic with N meningitidis presented with petechiae or purpura. All 13 children with occult bacteremia were sent home after blood cultures were obtained; six of the 13 received a regimen of oral amoxicillin for otitis media. At reexamination (interval 16 to 119 hours) four had meningitis, seven were clinically improved (afebrile, negative blood culture, without invasive disease), and two were still mildly febrile with negative blood culture. Three of these bacteremic children experienced spontaneous clinical and bacteriologic resolution without antibiotic treatment. This has not been previously reported.

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