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Evaluation of Host-Pathogen Responses and Vaccine Efficacy in Mice
Published on: February 22, 2019
[PERSISTENCE OF BORDETELLA PERTUSSIS BACTERIA AND A POSSIBLE MECHANISM OF ITS FORMATION]
Insights
Pertussis (whooping cough) is increasing globally, with atypical and asymptomatic cases common. Avirulent Bordetella pertussis mutants may explain persistent infections and transmission from vaccinated populations.
Area of Science:
- Microbiology
- Immunology
- Epidemiology
Background:
- Pertussis morbidity is rising globally despite mass vaccination efforts.
- Disease presentation is shifting towards atypical forms in adolescents and adults, with asymptomatic carriage prevalent.
- Infant infections predominantly originate from household contacts, highlighting the role of adult reservoirs.
Purpose of the Study:
- To investigate the changing epidemiology of pertussis.
- To explore the mechanisms behind Bordetella pertussis persistence and asymptomatic carriage.
- To understand the role of bacterial genetic changes in pertussis resurgence.
Main Methods:
- Analysis of Bordetella pertussis strains from human patients with typical and atypical pertussis.
- Experimental infection models in mice and monkeys to study bacterial invasion, survival, and population dynamics.
- Investigation of genetic factors, including IS-element integration into virulence genes like bvgAS operon.
Main Results:
- Atypical pertussis forms and asymptomatic carriage of Bordetella pertussis are widespread.
- Prolonged persistence of the causative agent has been identified.
- Accumulation of avirulent insertion Bvg mutants of B. pertussis was observed in experimental models and in healthy carriers (over 50%).
- Changes in circulating bacterial genotypes and the formation of persistent bacterial forms are linked to IS-element integration.
Conclusions:
- Reduced virulence in B. pertussis, potentially due to gene inactivation, facilitates long-term host persistence and the formation of healthy carriers.
- The rise in pertussis in developed nations using acellular vaccines may be linked to vaccines reducing disease severity but not preventing infection or carriage.
- Further research into bacterial persistence mechanisms is crucial for developing novel preventive strategies and vaccines.
Abstract:
A growth of pertussis morbidity is observed in many countries of the world against the background of mass vaccindtion. Forms of the disease course have changed. Atypical forms of pertussis occur predominately in adolescents and adults. Asymptomatic carriage of the causative agent has been established. Infection of infants with. BordetelIa pertussis bacteria in more than 90% of cases occurs from parents and relatives. A prolonged persistence of the causative agent has been identified. Morbidity increase in developed countries is associated with the use of acellular vaccines, that do not protect from the infection, but reduce severity of the disease. A change of genotypes of the circulating bacteria strains is observed ubiquitously. Formation of a persistent form of B. pertussis is possible due to a reversible integration of IS-elements into bvgAS operon and other virulence genes. The results of studies of invasion and survival of B. pertussis bacteria in eukaryotic cells, a change in B. pertussis bacteria population after experimental infection of laboratory mice and monkeys are presented, accumulation of avirulent insertion Bvg mutants of B. pertussis was detected. The data obtained are in accordance with the results of analysis of causative agent population in patients with typical and atypical forms of pertussis in humans. More than 50% of the population of B. pertussis bacteria in practically healthy carriers was shown to be presented by avirulent insertion Bvg mutants. B. pertussis virulence reducing as a result of inactivation of single or several virulence genes probably provide long-term persistence of bacteria in host organism and formation of apparently healthy vehicles. Follow-up studies on that front would help to formulate new attitudes to preventive measures of pertussis and lead to development of fundamentally new pharmaceuticals (vaccines) preventing formation of bacterial persistence.
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