Detection of avirulent insertional Bordetella pertussis bvg − mutants in patients with pertussis and with upper respiratory tract infection and in seemingly healthy people

Medkova, A. Yu.; Alyapkina, Yu. S.; Sinyashina, L. N.; Амелина, И. П.; Alekseev, Ya. I.; Боковой, А Г; Karataev, G. I.

doi:10.3103/s0891416810040051

Cited by 9 publications

(1 citation statement)

References 19 publications

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“…Most reports relate to the transition from bvg + (virulent under permissive conditions) to bvg – (avirulent), but the reversible nature of phase variation has been demonstrated [2–4]. Molecular mechanisms include the translocation of IS elements, insertions/deletions, DNA methylation, or point mutations [3–12]. They occur in regulatory or coding regions, and affect either the master virulence regulator (BvgAS), resulting in pleiotropic effects, or individual members of the BvgAS regulon [3, 6, 8, 13, 14].…”

Section: Introductionmentioning

confidence: 99%

A versatile, non genetically modified organism (GMO)‐based strategy for controlling low‐producer mutants in Bordetella pertussis cultures using antigenic modulation

Goffin

Slock

Smessaert

et al. 2015

Biotechnology Journal

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The uncontrolled presence of non‐producer mutants negatively affects bioprocesses. In Bordetella pertussis cultures, avirulent mutants emerge spontaneously and accumulate. We characterized the dynamics of accumulation using high‐throughput growth assays and competition experiments between virulent and avirulent (bvg–) isolates. A fitness advantage of bvg– cells was identified as the main driver for bvg– accumulation under conditions of high virulence factor production. Conversely, under conditions that reduce their expression (antigenic modulation), bvg– takeover could be avoided. A control strategy was derived, which consists in applying modulating conditions whenever virulence factor production is not required. It has a wide range of applications, from routine laboratory operations to vaccine manufacturing, where pertussis toxin yields were increased 1.4‐fold by performing early pre‐culture steps in modulating conditions. Because it only requires subtle modifications of the culture medium and does not involve genetic modifications, this strategy is applicable to any B. pertussis isolate, and should facilitate regulatory acceptance of process changes for vaccine production. Strategies based on the same concept, could be derived for other industrially relevant micro‐organisms. This study illustrates how a sound scientific understanding of physiological principles can be turned into a practical application for the bioprocess industry, in alignment with Quality by Design principles.

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