FEATURES OF BETA-LACTAMASE ACTIVITY IN FRANCISELLA TULARENSIS subsp. MEDIASIATICA

Small Gram-negative bacteria Francisella tularensis is the tularemia causative agent. This species subdivides on four subspecies — ssp. tularensis, holarctica, mediasiatica and novicida, which have some differences in their distribution areas, pathogenicity and epidemical potencial. Until recently o...

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Autores principales:	I. V. Bakhteeva, T. B. Kravchenko, A. K. Ryabko, G. M. Titareva, I. O. Lev, A. N. Mokrievich, V. S. Timofeev
Formato:	article
Lenguaje:	RU
Publicado:	Sankt-Peterburg : NIIÈM imeni Pastera 2018
Materias:	fransisella tularensis subspecies mediasiatica β-lactamase activity antibiotic resistance genes of β-lactamase genetic diversity Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/847466e7666d4746a9e455a92f570570
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spelling	oai:doaj.org-article:847466e7666d4746a9e455a92f5705702021-11-22T07:09:48ZFEATURES OF BETA-LACTAMASE ACTIVITY IN FRANCISELLA TULARENSIS subsp. MEDIASIATICA2220-76192313-739810.15789/2220-7619-2018-1-33-42https://doaj.org/article/847466e7666d4746a9e455a92f5705702018-05-01T00:00:00Zhttps://www.iimmun.ru/iimm/article/view/669https://doaj.org/toc/2220-7619https://doaj.org/toc/2313-7398Small Gram-negative bacteria Francisella tularensis is the tularemia causative agent. This species subdivides on four subspecies — ssp. tularensis, holarctica, mediasiatica and novicida, which have some differences in their distribution areas, pathogenicity and epidemical potencial. Until recently only subspecies holarctica was found on the territory of the Russian Federation, but in 2013 a natural focus of tularemia in which circulates F. tularensis subsp. mediasiatica was found on the Altai. Till now this subspecies was found only in Central Asia. The data of laboratory studies indicate the ability of strains of this subspecies to cause infection in rabbits and mice which is comparable in severity to infection caused by subsp. holarctica strains. However, the virulence of F. tularensis subsp. mediasiatica for humans and its epidemical potential are still unclear, since no cases of human infection caused by the strains of this subspecies have been recorded, probably due to the geographical aspects — mountainous Altai and Central Asia are extremely sparsely populated regions. The main phenotypic feature of this subspecies is the lack of activity of β-lactamase, which is responsible for the natural resistance to β-lactam antibiotics (penicillins, cephalosporins and carbapenems). Despite the absence of detectable enzymatic activity, subsp. mediasiatica strains are resistant to these antibiotics. In this article we report that subsp. mediasiatica strains have β-lactamase activity despite to current opinion, but the of β-lactams hydrolysis rate is much more lower in comparison with reaction rate of subs. holarctica strains. In addition, in case of a decrease of the microbial cells number in the nutrient medium, antibiotic susceptibility appears. We identified a single specific for subsp. mediasiatica nucleotide substitution G/A at the 290 position of the blaB gene, which encodes the active serine β-lactamase. This substitution leads to the amino acid substitution Gly/Arg at the 97 position of the protein BlaB. We assume, that enzymatic activity decreasing is the most likely caused by this substitution), for example it may cause some conformational changes leading either to enzyme — substrate affinity decreasing or to in the lifetime of the enzyme-substrate complex increasing. On the basis of the found nucleotide substitution, we developed an allele-specific PCR test that makes it possible to determine whether the studied strain F. tularensis belongs to the subspecies mediasiatica.I. V. BakhteevaT. B. KravchenkoA. K. RyabkoG. M. TitarevaI. O. LevA. N. MokrievichV. S. TimofeevSankt-Peterburg : NIIÈM imeni Pasteraarticlefransisella tularensissubspecies mediasiaticaβ-lactamase activityantibiotic resistancegenes of β-lactamasegenetic diversityInfectious and parasitic diseasesRC109-216RUInfekciâ i Immunitet, Vol 8, Iss 1, Pp 33-42 (2018)
institution	DOAJ
collection	DOAJ
language	RU
topic	fransisella tularensis subspecies mediasiatica β-lactamase activity antibiotic resistance genes of β-lactamase genetic diversity Infectious and parasitic diseases RC109-216
spellingShingle	fransisella tularensis subspecies mediasiatica β-lactamase activity antibiotic resistance genes of β-lactamase genetic diversity Infectious and parasitic diseases RC109-216 I. V. Bakhteeva T. B. Kravchenko A. K. Ryabko G. M. Titareva I. O. Lev A. N. Mokrievich V. S. Timofeev FEATURES OF BETA-LACTAMASE ACTIVITY IN FRANCISELLA TULARENSIS subsp. MEDIASIATICA
description	Small Gram-negative bacteria Francisella tularensis is the tularemia causative agent. This species subdivides on four subspecies — ssp. tularensis, holarctica, mediasiatica and novicida, which have some differences in their distribution areas, pathogenicity and epidemical potencial. Until recently only subspecies holarctica was found on the territory of the Russian Federation, but in 2013 a natural focus of tularemia in which circulates F. tularensis subsp. mediasiatica was found on the Altai. Till now this subspecies was found only in Central Asia. The data of laboratory studies indicate the ability of strains of this subspecies to cause infection in rabbits and mice which is comparable in severity to infection caused by subsp. holarctica strains. However, the virulence of F. tularensis subsp. mediasiatica for humans and its epidemical potential are still unclear, since no cases of human infection caused by the strains of this subspecies have been recorded, probably due to the geographical aspects — mountainous Altai and Central Asia are extremely sparsely populated regions. The main phenotypic feature of this subspecies is the lack of activity of β-lactamase, which is responsible for the natural resistance to β-lactam antibiotics (penicillins, cephalosporins and carbapenems). Despite the absence of detectable enzymatic activity, subsp. mediasiatica strains are resistant to these antibiotics. In this article we report that subsp. mediasiatica strains have β-lactamase activity despite to current opinion, but the of β-lactams hydrolysis rate is much more lower in comparison with reaction rate of subs. holarctica strains. In addition, in case of a decrease of the microbial cells number in the nutrient medium, antibiotic susceptibility appears. We identified a single specific for subsp. mediasiatica nucleotide substitution G/A at the 290 position of the blaB gene, which encodes the active serine β-lactamase. This substitution leads to the amino acid substitution Gly/Arg at the 97 position of the protein BlaB. We assume, that enzymatic activity decreasing is the most likely caused by this substitution), for example it may cause some conformational changes leading either to enzyme — substrate affinity decreasing or to in the lifetime of the enzyme-substrate complex increasing. On the basis of the found nucleotide substitution, we developed an allele-specific PCR test that makes it possible to determine whether the studied strain F. tularensis belongs to the subspecies mediasiatica.
format	article
author	I. V. Bakhteeva T. B. Kravchenko A. K. Ryabko G. M. Titareva I. O. Lev A. N. Mokrievich V. S. Timofeev
author_facet	I. V. Bakhteeva T. B. Kravchenko A. K. Ryabko G. M. Titareva I. O. Lev A. N. Mokrievich V. S. Timofeev
author_sort	I. V. Bakhteeva
title	FEATURES OF BETA-LACTAMASE ACTIVITY IN FRANCISELLA TULARENSIS subsp. MEDIASIATICA
title_short	FEATURES OF BETA-LACTAMASE ACTIVITY IN FRANCISELLA TULARENSIS subsp. MEDIASIATICA
title_full	FEATURES OF BETA-LACTAMASE ACTIVITY IN FRANCISELLA TULARENSIS subsp. MEDIASIATICA
title_fullStr	FEATURES OF BETA-LACTAMASE ACTIVITY IN FRANCISELLA TULARENSIS subsp. MEDIASIATICA
title_full_unstemmed	FEATURES OF BETA-LACTAMASE ACTIVITY IN FRANCISELLA TULARENSIS subsp. MEDIASIATICA
title_sort	features of beta-lactamase activity in francisella tularensis subsp. mediasiatica
publisher	Sankt-Peterburg : NIIÈM imeni Pastera
publishDate	2018
url	https://doaj.org/article/847466e7666d4746a9e455a92f570570
work_keys_str_mv	AT ivbakhteeva featuresofbetalactamaseactivityinfrancisellatularensissubspmediasiatica AT tbkravchenko featuresofbetalactamaseactivityinfrancisellatularensissubspmediasiatica AT akryabko featuresofbetalactamaseactivityinfrancisellatularensissubspmediasiatica AT gmtitareva featuresofbetalactamaseactivityinfrancisellatularensissubspmediasiatica AT iolev featuresofbetalactamaseactivityinfrancisellatularensissubspmediasiatica AT anmokrievich featuresofbetalactamaseactivityinfrancisellatularensissubspmediasiatica AT vstimofeev featuresofbetalactamaseactivityinfrancisellatularensissubspmediasiatica
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FEATURES OF BETA-LACTAMASE ACTIVITY IN FRANCISELLA TULARENSIS subsp. MEDIASIATICA

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