Russian isolates enlarge the known geographic diversity of Francisella tularensis subsp. mediasiatica

Abstract

Francisella tularensis, a small Gram-negative bacterium, is capable of infecting a wide range of animals, including humans, and causes a plague-like disease called tularemia—a highly contagious disease with a high mortality rate. Because of these characteristics, F. tularensis is considered a potential agent of biological terrorism. Currently, F. tularensis is divided into four subspecies, which differ in their virulence and geographic distribution. Two of them, subsp. tularensis (primarily found in North America) and subsp. holarctica (widespread across the Northern Hemisphere), are responsible for tularemia in humans. Subsp. novicida is almost avirulent in humans. The fourth subspecies, subsp. mediasiatica, is the least studied because of its limited distribution and impact in human health. It is found only in sparsely populated regions of Central Asia. In this report, we describe the first focus of naturally circulating F. tularensis subsp. mediasiatica in Russia. We isolated and characterized 18 strains of this subspecies in the Altai region. All strains were highly virulent in mice. The virulence of subsp. mediasiatica in a vaccinated mouse model is intermediate between that of subsp. tularensis and subsp. holarctica. Based on a multiple-locus variable number tandem repeat analysis (MLVA), we show that the Altaic population of F. tularensis subsp. mediasiatica is genetically distinct from the classical Central Asian population, and probably is endemic to Southern Siberia. We propose to subdivide the mediasiatica subspecies into three phylogeographic groups, M.I, M.II and M.III.

Galleria mellonella Reveals Niche Differences Between Highly Pathogenic and Closely Related Strains of Francisella spp.

“…lethality in G. mellonella generated in this study and previously published data on Francisella spp. lethality in mice by subcutaneous or intracutaneous inoculation (Bell et al, 1955 ; Owen et al, 1964 ; Guryčová, 1998 ; Kieffer et al, 2003 ; Salomonsson et al, 2009 ; Molins et al, 2014 ; Propst et al, 2016 ; Timofeev et al, 2017 ) and severity of disease in humans (Saslaw et al, 1961a , b ; Dienst, 1963 ; Kugeler et al, 2009 ). Lethality of the different Francisella strains in G. mellonella (larvae death within 3 days, infectious dose 10 6 bacteria/mL) and mice (LD 50 < 10 3 ) was scored as high lethality (red), intermediate lethality (larvae death > 3 days, LD 50 mice > 10 3 ) (orange) and non-lethal (green).…”

“…Severity of disease caused by the Francisella strains in humans, was scored as incapacitating disease in humans (red), causing disease only in humans with a compromised immune response or underlying health defects (yellow) and non-virulent (green). There is only limited data on the virulence of F. t. mediasiatica in humans (Timofeev et al, 2017 ) (striped) and data on F. hispaniensis and F. endociliophora lethality in mice are lacking. The LVS strain is a live attenuated strain that was selected for vaccination in humans but still remains unlicensed for human use (Sandström, 1994 ).…”

“…Both F. tularensis subspecies holarctica and subspecies tularensis cause disease in humans (Penn, 2010 ). However, information on the virulence of F. t. mediasiatica , which is primarily found in Central Asia, in humans is limited (Timofeev et al, 2017 ). Besides F. tularensis , the genus Francisella also includes opportunistic pathogens that only cause disease in immunocompromised humans (i.e., F. novicida, F. hispaniensis and F. philomiragia ; Larson et al, 1955 ; Olsufjev et al, 1959 ; Hollis et al, 1989 ; Huber et al, 2010 ; Penn, 2010 ; Aravena-Román et al, 2015 ).…”

Molecular Survey of Tularemia and Plague in Small Mammals From Iran

“…The current knowledge, however, suggests that subsp. mediasiatica is rare in these geographical areas, which are located relatively distant to Iran (Timofeev et al, 2017 ).…”

Phylogenetic Lineages of Francisella tularensis in Animals

“…F. tularensis subsp. mediasiatica was recently divided into three clades: M.I, M.II, and M.III (Timofeev et al, 2017 ). However, bias inherent to the evolution of VNTRs does not permit solid phylogenetic studies since these markers are prone to homoplasy resulting from convergent evolution.…”