Meningococcal Disease Is a Very Serious Infection Caused by The

Total Page:16

File Type:pdf, Size:1020Kb

Meningococcal Disease Is a Very Serious Infection Caused by The Meningococcal Disease Janet Groth, MS, CFNP eningococcal disease is a very serious infection caused by the bacterium Neisseria meningitidis. Meningococcus is now the second most common Mcause of bacterial meningitis among children and the third leading cause among adults. Despite advances in antibiotics, the overall mortality in the USA is 13%. Meningococcus has a particular affinity for the infection follows a fulminant course, known as bloodstream and the lining around the brain, called Waterhouse-Friedrichsen Syndrome. This rapidly the meninges. The severity of infection ranges from progressive disease, marked by hemorrhages into the a transient fever with bacteremia to severe life- skin, joints, and internal organs, can lead to septic threatening illness. Infrequently, meningococcal shock and death even when appropriate antibiotics infection causes pneumonia or conjunctivitis. are started immediately. The clinical syndrome of meningococcal A positive outcome of meningococcal disease infection is similar to other types of meningitis. depends on prompt diagnosis, early referral, and Symptoms may first appear as a respiratory tract rapid treatment with antibiotics. illness, often followed by the abrupt onset of fever, headache, stiff neck, and vomiting. Changes in Prevalence and Distribution mental status may ensue, including confusion, Endemic disease is most common in children drowsiness, stupor, and even coma. Infants may under the age of 5, particularly within the 6-12 have fever with irritability, poor feeding, vomiting, month age group. Outbreaks are common among or a high-pitched cry. school age children and young adults in group Waterhouse- Friedrichsen A specific feature in the presentation of settings, such as day care centers, military camps, Syndrome. meningococcal disease is the appearance of tiny and colleges. Freshman college students living in This rapidly hemorrhages, called petechiae. These are usually dormitories are at particular risk. This infection progressive form found on the trunk and lower extremities. Petechiae appears to be seasonal, with the majority of cases of meningococcal are present in 75% of patients with meningococcal occurring in winter and early spring. disease is marked by hemorrhages into the infection. skin and joints. Septic Meningococcal infection is associated with high Transmission shock and death rates of morbidity and mortality. Even with optimal Neisseria meningitidis spreads when carriers can result, even medical care and appropriate treatment, almost one cough or sneeze infected secretions into the air that with appropriate antibiotics. in ten patients die from this disease, while as many as others inhale. The disease also spreads through Photo courtesy 20% are left with hearing loss, neurological impair- infected nose and throat secretions that come into of the ment, or loss of a limb. In rare cases, meningococcal contact with the mucous membranes of others. Meningitis Trust The Health Care of Homeless Persons - Part I - Meningococcal Disease 89 The onset of disease usually occurs within 10 days tory tract fluids to destroy the organism at the site (commonly 3-4 days), although longer intervals are of colonization in the nasopharynx. To eradicate the possible. organism completely, patients treated with these Meningococcus inhabits the upper respiratory antibiotics should also be treated with an antibiotic tract of a significant proportion of individuals that is known to clear the nasopharynx of organ- without causing illness. It is not known why some isms, namely ciprofloxacin, ceftriaxone, or rifampin. who carry invasive strains of the bacteria become ill Ciprofloxacin (Cipro™) 500 mg in a single oral while others do not. Some speculate that a concur- dose can be given to adults but is not recommended rent viral infection or exposure to passive or active for children under age 18 unless there is no alterna- cigarette smoke may diminish a person’s resistance tive therapy. It is not recommended for pregnant or to Neisseria meningitidis that has colonized a lactating women. person’s upper respiratory tract, thus allowing illness Ceftriaxone (Rocephin™) in a one-time dose to develop in someone who has been carrying the at 125 mg for children less than age 15 and 250 mg organism. Persons with certain immune deficiencies for those ages 15 and above is an alternative course and persons without a spleen may be at increased of therapy. risk for infection. Rifampin (Rimactane™, Rifadin™) is a drug that has long been used to eradicate meningococcal Diagnosis colonization. Dosing is 5 mg/kg every 12 hours for Anyone suspected of meningococcal disease 2 days in infants less than 1 month old, 10 mg/kg should have blood cultures and a lumbar puncture of body weight with a maximum of 600 mg every without delay. The organism may also be cultured 12 hours for two days in all persons older than one from synovial, pleural, or pericardial fluid. month. For infants, the liquid form of rifampin is easier to administer. If liquid rifampin is unavail- Treatment able, the contents of the capsules can be mixed with Meningococcal Disease applesauce. Rifampin cannot be given to pregnant Persons suspected of having meningococcal women or those with active liver disease. disease require intravenous antibiotic therapy and Urine, stool, sweat, tears, and semen may turn close supervision in a hospital setting. The disease orange-red when taking rifampin. Soft contact calls for strict respiratory isolation for at least 24 lenses can be permanently stained, so glasses should hours after the beginning of antibiotic therapy. A be worn while taking the medication. Rifampin third generation cephalosporin such as ceftriaxone may also diminish the effects of methadone and the (Rocephin™) in high doses is usually used initially effectiveness of birth control pills. Patients should to treat the infection. High doses of penicillin G or use a barrier form of contraception (condoms, chloramphenicol for 1 to 2 weeks have also success- diaphragm) for the duration of the entire birth fully treated this infection. control pill cycle in which rifampin therapy occurs. Colonization Antibiotics other than ceftriaxone usually used Prevention and Control to treat meningococcal infection do not reliably All persons who have been in close contact with reach high enough concentrations in upper respira- a person with meningococcal disease should receive antibiotic prophylaxis with ciprofloxacin, rifampin, or ceftriaxone. The risk of developing disease from Rash from such contact varies with the duration and closeness Meningococcus. A characteristic of exposure. In general, persons with less than 20 feature is the hours of contact in the week prior to illness are likely appearance of tiny to be at less risk than those with a longer duration hemorrhages on the of contact. However, persons with direct mucous skin, called petechiae. When glass is membrane exposure to secretions from an infected pressed against the person’s nose or throat are at higher risk. Such types skin, the petechiae of exposure include: do not blanche or • mouth-to-mouth resuscitation; lose their color. • kissing; Photo courtesy of the Meningitis Trust • mouthing toys; • sharing food, glasses, bottles, or cigarettes. 90 The Health Care of Homeless Persons - Part I - Meningococcal Disease The Health Care of Homeless Persons - Part I - Meningococcal Disease 91 Identified close contacts should be evaluated for linings covering the brain). This illness can be life rifampin, ciprofloxacin, or ceftriaxone prophylaxis threatening and occurs most commonly in infants within 24 hours of exposure. Refer to the treatment and young adults. section above for dosages. If antibiotics cannot be Initial symptoms can be similar to an upper initiated within 10 days of exposure, the efficacy is respiratory tract illness, followed by the abrupt diminished. onset of fever, headaches, stiff neck, vomiting, and Due to the emergence of resistant strains of occasionally a change in behavior. Infants may have Neisseria meningitidis and possible non-adherence a fever, appear irritable, have a high-pitched cry, and with recommended antibiotic prophylaxis, care- feed poorly. Petechiae, or tiny hemorrhages into the givers should monitor all close contacts for at least skin, may appear on the trunk or legs in both adults 2 weeks following the diagnosis of the initial case. and children. We recommend that smaller shelters, where families The spread of meningococcal disease occurs or adults live for weeks or months, hold any new when infected individuals cough or sneeze into admissions until all identified persons at risk within air that is then inhaled by others. Direct exposure the shelter have received prophylaxis with ciproflox- to an infected person’s saliva will also spread this acin, rifampin, or ceftriaxone. If compliance with infection. therapy cannot be assured, then admissions should Those suspected of having meningococcal further be held until 2 weeks following the diagnosis disease must be evaluated as soon as possible in an of the last case of meningococcal disease. Any close acute care setting. Respiratory isolation, antibiotic contact who develops a febrile illness should go to therapy, and close monitoring are required. an acute care facility immediately for evaluation. Persons likely to be at greatest risk from expo- Staff or caregivers should notify the facility ahead of sure include those who have spent 20 or more hours time to ensure that precautions are taken to lessen
Recommended publications
  • African Meningitis Belt
    WHO/EMC/BAC/98.3 Control of epidemic meningococcal disease. WHO practical guidelines. 2nd edition World Health Organization Emerging and other Communicable Diseases, Surveillance and Control This document has been downloaded from the WHO/EMC Web site. The original cover pages and lists of participants are not included. See http://www.who.int/emc for more information. © World Health Organization This document is not a formal publication of the World Health Organization (WHO), and all rights are reserved by the Organization. The document may, however, be freely reviewed, abstracted, reproduced and translated, in part or in whole, but not for sale nor for use in conjunction with commercial purposes. The views expressed in documents by named authors are solely the responsibility of those authors. The mention of specific companies or specific manufacturers' products does no imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. CONTENTS CONTENTS ................................................................................... i PREFACE ..................................................................................... vii INTRODUCTION ......................................................................... 1 1. MAGNITUDE OF THE PROBLEM ........................................................3 1.1 REVIEW OF EPIDEMICS SINCE THE 1970S .......................................................................................... 3 Geographical distribution
    [Show full text]
  • Meningococcal Meningitis (Neisseria Meningitidis)
    Division of Disease Control What Do I Need To Know? Meningococcal Meningitis (Neisseria meningitidis) What is meningococcal meningitis ? Meningitis is a severe infection of the bloodstream and meninges (a thin lining covering the brain and spinal cord) caused by a bacteria or virus. Bacterial meningitis is usually more severe than viral meningitis but is less common. Bacterial meningitis is most commonly caused by Haemophilus influenzae type B, Streptococcus pneumoniae or Neisseria meningitidis. The most severe form of bacterial meningitis is called Neisseria meningitidis. It is a relatively rare disease and usually occurs as a single isolated event. Clusters of cases or outbreaks are rare in the United States. Who is at risk for meningococcal meningitis? Anyone can get meningococcal meningitis, but it is more common in infants and children. Other people at increased risk for meningitis are college freshmen living in dormitories, microbiologists who are routinely exposed, military recruits, and travelers to areas where meningitis occurs frequently, such as sub-Saharan Africa. What are the symptoms of meningococcal meningitis? Although most people exposed to the meningococcal bacteria do not become seriously ill, some may develop fever, headache, vomiting, stiff neck and a rash. Meningitis can cause sensitivity to light, confusion, drowsiness, seizures and sometimes coma. The disease is sometimes fatal. How soon do symptoms appear? The symptoms may appear one to 10 days after exposure, but usually less than four days. How is meningococcal meningitis spread? Meningococcal meningitis is spread by direct, close contact with nasal or throat discharges of an infected person. Many people carry meningococcal bacteria in their nose and throat without any signs of illness, while others may develop serious symptoms.
    [Show full text]
  • Functional Genomics of Neisseria Meningitidis Pathogenesis
    © 2000 Nature America Inc. • http://medicine.nature.com ARTICLES Functional genomics of Neisseria meningitidis pathogenesis YAO-HUI SUN1, SHARMILA BAKSHI1, RONALD CHALMERS2 & CHRISTOPH M. TANG1 1University Department of Paediatrics, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom 2Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom Correspondence to be addressed to C.M.T.; Email: [email protected] and R.C.; Email: [email protected] The pathogenic bacterium Neisseria meningitidis is an important containing unique signature tags (fig, 1b), in 96 separate trans- cause of septicemia and meningitis, especially in childhood1. The position reactions. The modified genomic DNA was repaired, establishment and maintenance of bacteremic infection is a pre- and returned to the host by transformation. We selected 30 mu- requisite for all the pathological sequelae of meningococcal in- tants from each reaction, resulting in a library of 2,880 mutants fection. To further understand the genetic basis of this essential (30 pools × 96). To determine whether Tn10 insertion occurs at step in pathogenesis, we analyzed a library of 2,850 insertional diverse sites, we assessed 40 transformants from a single trans- .com mutants of N. meningitidis for their capacity to cause systemic in- position reaction by Southern blot analysis. Each had a single, fection in an infant rat model. The library was constructed by in distinct Tn10 insertion (Fig. 1c). To establish whether Tn10 in- .nature vitro modification of Neisseria genomic DNA with the purified tegration was stable during systemic infection of infant rats, we components of Tn10 transposition2.
    [Show full text]
  • Atypical, Yet Not Infrequent, Infections with Neisseria Species
    pathogens Review Atypical, Yet Not Infrequent, Infections with Neisseria Species Maria Victoria Humbert * and Myron Christodoulides Molecular Microbiology, School of Clinical and Experimental Sciences, University of Southampton, Faculty of Medicine, Southampton General Hospital, Southampton SO16 6YD, UK; [email protected] * Correspondence: [email protected] Received: 11 November 2019; Accepted: 18 December 2019; Published: 20 December 2019 Abstract: Neisseria species are extremely well-adapted to their mammalian hosts and they display unique phenotypes that account for their ability to thrive within niche-specific conditions. The closely related species N. gonorrhoeae and N. meningitidis are the only two species of the genus recognized as strict human pathogens, causing the sexually transmitted disease gonorrhea and meningitis and sepsis, respectively. Gonococci colonize the mucosal epithelium of the male urethra and female endo/ectocervix, whereas meningococci colonize the mucosal epithelium of the human nasopharynx. The pathophysiological host responses to gonococcal and meningococcal infection are distinct. However, medical evidence dating back to the early 1900s demonstrates that these two species can cross-colonize anatomical niches, with patients often presenting with clinically-indistinguishable infections. The remaining Neisseria species are not commonly associated with disease and are considered as commensals within the normal microbiota of the human and animal nasopharynx. Nonetheless, clinical case reports suggest that they can behave as opportunistic pathogens. In this review, we describe the diversity of the genus Neisseria in the clinical context and raise the attention of microbiologists and clinicians for more cautious approaches in the diagnosis and treatment of the many pathologies these species may cause. Keywords: Neisseria species; Neisseria meningitidis; Neisseria gonorrhoeae; commensal; pathogenesis; host adaptation 1.
    [Show full text]
  • Neisseria Meningitidis
    Influence of host and bacterial factors during Neisseria meningitidis colonization Sara Sigurlásdóttir Academic dissertation for the Degree of Doctor of Philosophy in Molecular Bioscience at Stockholm University to be publicly defended on Tuesday 18 December 2018 at 10.00 in Vivi Täckholm-salen (Q-salen), NPQ-huset, Svante Arrhenius vä g 20. Abstract The human-restricted pathogen Neisseria meningitidis is a major cause of bacterial meningitis and sepsis worldwide. Colonization of the mucosal layer in the upper respiratory tract is essential to establish an asymptomatic carrier state and invasive disease. N. meningitidis encounters diverse environmental challenges during colonization and has evolved multiple strategies and virulence factors to survive and adapt within the host. Upon initial adhesion to the host epithelial cells, N. meningitidis forms pilus-mediated aggregates called microcolonies, which are characterized by interbacterial and host-cell interactions. Microcolonies promote long-term asymptomatic colonization within the host. However, the dispersal of single bacteria from microcolonies can help N. meningitidis to develop close contact with host cells and facilitate the invasion of mucosal surfaces or transmission to a new host. This thesis focuses on understanding how the interplay between the host, environment, and virulence factors influences N. meningitidis colonization. Paper I shows that the host-derived metabolite lactate induces rapid dispersal of N. meningitidis microcolonies. Further molecular characterization in Paper II revealed that lactate-induced dispersal is mediated by pilus retraction, occurs in a density-dependent manner, and is responsive to temperature. Paper III shows that the deletion of D-lactate dehydrogenase LdhA in N. meningitidis promotes aggregation and biofilm formation through an increase in the autolysis-mediated release of extracellular DNA.
    [Show full text]
  • Pathophysiology of Meningococcal Meningitis and Septicaemia N Pathan, S N Faust, M Levin
    601 CURRENT TOPIC Arch Dis Child: first published as 10.1136/adc.88.7.601 on 1 July 2003. Downloaded from Pathophysiology of meningococcal meningitis and septicaemia N Pathan, S N Faust, M Levin ............................................................................................................................. Arch Dis Child 2003;88:601–607 Neisseria meningitidis is remarkable for the diversity of The human immune system has a number of interactions that the bacterium has with the human host, different mechanisms to limit the growth of meningococci in blood. Both the older innate ranging from asymptomatic nasopharyngeal immune system and acquired immunity through colonisation affecting virtually all members of the antibodies, T and B cells play a role. The population; through focal infections of the meninges, epidemiology of meningococcal disease clearly indicates that the development of specific anti- joints, or eye; to the devastating and often fatal body is the most important immunoprotective syndrome of meningococcal septic shock and purpura mechanism.78 The peak incidence of the disease fulminans. occurs in the first year of life following the loss of maternal antibody; the disease becomes progres- .......................................................................... sively less common throughout childhood and is extremely rare in adults, a pattern suggestive of a n the past few decades, considerable progress major role for acquired immunity through anti- has been made in understanding the complex bodies. The studies
    [Show full text]
  • Bacterial Meningitis Epidemiology in 5 Countries in the Meningitis Belt of Sub-Saharan Africa, 2015–2017
    HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author J Infect Manuscript Author Dis. Author manuscript; Manuscript Author available in PMC 2020 October 31. Published in final edited form as: J Infect Dis. 2019 October 31; 220(Suppl 4): S165–S174. doi:10.1093/infdis/jiz358. Bacterial meningitis epidemiology in 5 countries in the meningitis belt of sub-Saharan Africa, 2015–2017 Heidi M. Soeters1, Alpha Oumar Diallo1, Brice W. Bicaba2, Goumbi Kadadé3, Assétou Y. Dembélé4, Mahamat A. Acyl5, Christelle Nikiema6, Adodo Yao Sadji6, Alain N. Poy7, Clement Lingani8, Haoua Tall9, Souleymane Sakandé9, Félix Tarbangdo10, Flavien Aké10, Sarah A. Mbaeyi1, Jennifer Moïsi11,a, Marietou F. Paye1, Yibayiri Osee Sanogo1, Jeni T. Vuong1, Xin Wang1, Olivier Ronveaux12, Ryan T. Novak1, MenAfriNet Consortium* 1National Center for Immunization and Respiratory Diseases, CDC, Atlanta, GA, USA; 2Ministère de la Santé du Burkina Faso, Ouagadougou, Burkina Faso; 3Ministère de la Santé Publique du Niger, Niamey, Niger; 4Ministère de la Santé et de l’Hygiène Publique, Bamako, Mali; 5Ministère de la Santé Publique du Tchad, N’Djamena, Tchad; 6Ministère de la Santé et de la Protection Sociale du Togo, Lomé, Togo; 7World Health Organization Regional Office for Africa, Brazzaville, Republic of the Congo; 8World Health Organization, AFRO Intercountry Support Team for West Africa, Ouagadougou, Burkina Faso; 9Agence de Médicine Préventive, Ouagadougou, Burkina Faso; 10Davycas International, Ouagadougou, Burkina Faso; 11Agence de Médicine Préventive, Paris, France; 12World Health Organization, Geneva, Switzerland. Abstract Background: The MenAfriNet Consortium supports strategic implementation of case-based meningitis surveillance in key high-risk countries of the African meningitis belt: Burkina Faso, Chad, Mali, Niger, and Togo.
    [Show full text]
  • Virulence Factors of Meningitis-Causing Bacteria: Enabling Brain Entry Across the Blood–Brain Barrier
    International Journal of Molecular Sciences Review Virulence Factors of Meningitis-Causing Bacteria: Enabling Brain Entry across the Blood–Brain Barrier Rosanna Herold, Horst Schroten and Christian Schwerk * Department of Pediatrics, Pediatric Infectious Diseases, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany; [email protected] (R.H.); [email protected] (H.S.) * Correspondence: [email protected]; Tel.: +49-621-383-3466 Received: 26 September 2019; Accepted: 25 October 2019; Published: 29 October 2019 Abstract: Infections of the central nervous system (CNS) are still a major cause of morbidity and mortality worldwide. Traversal of the barriers protecting the brain by pathogens is a prerequisite for the development of meningitis. Bacteria have developed a variety of different strategies to cross these barriers and reach the CNS. To this end, they use a variety of different virulence factors that enable them to attach to and traverse these barriers. These virulence factors mediate adhesion to and invasion into host cells, intracellular survival, induction of host cell signaling and inflammatory response, and affect barrier function. While some of these mechanisms differ, others are shared by multiple pathogens. Further understanding of these processes, with special emphasis on the difference between the blood–brain barrier and the blood–cerebrospinal fluid barrier, as well as virulence factors used by the pathogens, is still needed. Keywords: bacteria; blood–brain barrier; blood–cerebrospinal fluid barrier; meningitis; virulence factor 1. Introduction Bacterial meningitis, as are bacterial encephalitis and meningoencephalitis, is an inflammatory disease of the central nervous system (CNS). It can be diagnosed by the presence of bacteria in the CNS.
    [Show full text]
  • Meningococcal Disease
    Meningococcal Disease What is meningococcal disease? Meningococcal disease is caused by bacteria called Neisseria meningitidis. It can lead to serious blood infections. When the linings of the brain and spinal cord become infected, it is called meningitis. The disease strikes quickly and can have serious complications, including death. Anyone can get meningococcal disease. Some people are at higher risk. This disease occurs more often in people who are: • Teenagers or young adults • Infants younger than one year of age • Living in crowded settings, such as college dormitories or military barracks • Traveling to areas outside of the United States, such as the “meningitis belt” in Africa • Living with a damaged spleen or no spleen or have sickle cell disease • Being treated with the medication Soliris® or, who have complement component deficiency (an inherited immune disorder) • Exposed during an outbreak • Working with meningococcal bacteria in a laboratory What are the symptoms? Symptoms appear suddenly – usually 3 to 4 days after a person is infected. It can take up to 10 days to develop symptoms. Symptoms may include: • A sudden high fever • Headache • Stiff neck (meningitis) • Nausea and vomiting • Red-purple skin rash • Weakness and feeling very ill • Eyes sensitive to light How is meningococcal disease spread? It spreads from person-to-person by coughing or coming into close or lengthy contact with someone who is sick or who carries the bacteria. Contact includes kissing, sharing drinks, or living together. Up to one in 10 people carry meningococcal bacteria in their nose or throat without getting sick. Is there treatment? Early diagnosis of meningococcal disease is very important.
    [Show full text]
  • Meningococcal Vaccines: Current Status and Emerging Strategies
    Review Meningococcal Vaccines: Current Status and Emerging Strategies Pumtiwitt C. McCarthy *, Abeer Sharyan and Laleh Sheikhi Moghaddam Department of Chemistry, Morgan State University, Baltimore, MD 21251, USA; [email protected] (A.S.); [email protected] (L.S.M.) * Correspondence: [email protected] ; Tel.: +1‐443‐885‐3882 Received: 30 January 2018; Accepted: 23 February 2018; Published: 25 February 2018 Abstract: Neisseria meningitidis causes most cases of bacterial meningitis. Meningococcal meningitis is a public health burden to both developed and developing countries throughout the world. There are a number of vaccines (polysaccharide‐based, glycoconjugate, protein‐based and combined conjugate vaccines) that are approved to target five of the six disease‐causing serogroups of the pathogen. Immunization strategies have been effective at helping to decrease the global incidence of meningococcal meningitis. Researchers continue to enhance these efforts through discovery of new antigen targets that may lead to a broadly protective vaccine and development of new methods of homogenous vaccine production. This review describes current meningococcal vaccines and discusses some recent research discoveries that may transform vaccine development against N. meningitidis in the future. Keywords: Neisseria meningitidis; glycoconjugate vaccines; protein‐based vaccines; vaccine development 1. Introduction Neisseria meningitidis is a leading cause of bacterial meningitis. According to the World Health Organization, the disease has a high mortality rate (up to 50% if left untreated) and can leave 10% of those who do survive with devastating sequelae such as deafness and loss of limbs [1]. Most cases of the disease affect children under the age of 2 and between the ages of 16–21 [2].
    [Show full text]
  • Pathogenic Neisseriae: Surface Modulation, Pathogenesis and Infection Control
    REVIEWS Pathogenic neisseriae: surface modulation, pathogenesis and infection control Mumtaz Virji Abstract | Although renowned as a lethal pathogen, Neisseria meningitidis has adapted to be a commensal of the human nasopharynx. It shares extensive genetic and antigenic similarities with the urogenital pathogen Neisseria gonorrhoeae but displays a distinct lifestyle and niche preference. Together, they pose a considerable challenge for vaccine development as they modulate their surface structures with remarkable speed. Nonetheless, their host-cell attachment and invasion capacity is maintained, a property that could be exploited to combat tissue infiltration. With the primary focus on N. meningitidis, this Review examines the known mechanisms used by these pathogens for niche establishment and the challenges such mechanisms pose for infection control. Neisseria meningitidis (meningococcus) and Neisseria surface variation also poses a substantial problem in gonorrhoeae (gonococcus), the well known agents of developing effective vaccines against several strains of epidemic meningitis and gonorrhoea, respectively, are N. meningitidis and against N. gonorrhoeae. Although related Gram-negative bacteria that specifically infect multicomponent vaccines are being developed, the humans; both pathogens prefer to inhabit distinct available vaccines fall short of combating all virulent human mucosal niches and cause markedly different strains7,8. diseases (FIG. 1). One important difference between the An array of molecules is produced by bacteria pathogens is that almost all clinically important N. men- to enable them to colonize and/or infect the host, ingitidis strains are encapsulated, whereas N. gonorrhoeae including adhesins, which are key factors that are strains lack capsule biosynthetic genes. N. meningitidis required for initial colonization of human mucosal is a frequent asymptomatic colonizer of the human sites.
    [Show full text]
  • Construction of a Complete Set of Neisseria Meningitidis Defined Mutants – The
    bioRxiv preprint doi: https://doi.org/10.1101/2020.08.12.247981; this version posted August 12, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Construction of a complete set of Neisseria meningitidis defined mutants – the 2 NeMeSys collection – and its use for the phenotypic profiling of the genome of 3 an important human pathogen 4 5 Alastair Muir1, Ishwori Gurung1, Ana Cehovin1, Adelme Bazin2, David Vallenet2, 6 Vladimir Pelicic1,* 7 8 1MRC Centre for Molecular Bacteriology and Infection, Imperial College London, 9 London, United Kingdom 10 11 2LABGeM, Génomique Métabolique, CEA, Genoscope, Institut François Jacob, 12 Université d’Evry, Université Paris-Saclay, CNRS, Evry, France 13 14 *Corresponding author 15 E-mail: [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.08.12.247981; this version posted August 12, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 16 Abstract 17 One of the most important challenges in biology is to determine the function of 18 millions of genes of unknown function. Even in model bacterial species, there is a 19 sizeable proportion of such genes, which has important theoretical and practical 20 consequences. Here, we constructed a complete collection of defined mutants – 21 named NeMeSys – in the important human pathogen Neisseria meningitidis, 22 consisting of individual mutants in 1,584 non-essential genes. This effort identified 23 391 essential meningococcal genes – highly conserved in other bacteria – leading to 24 a full panorama of the minimal genome in this species, associated with just four 25 underlying basic biological functions: 1) expression of genome information, 2) 26 preservation of genome information, 3) cell membrane structure/function, and 4) 27 cytosolic metabolism.
    [Show full text]