The Divergent Intracellular Lifestyle of Francisella tularensis in Evolutionarily Distinct Host Cells

Ožanič, Mateja; Marečić, Valentina; Kwaik, Yousef Abu; Šantić, Marina

doi:10.1371/journal.ppat.1005208

Cited by 35 publications

(21 citation statements)

References 38 publications

(57 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, due to the fastidious nature of this organism, it is unlikely capable of replication in the absence of essential host factors. Therefore, the increased resistance to Gm at lower environmental temperatures demonstrated here may provide an advantage until F. tularensis is phagocytosed or engulfed by a protozoan or arthropod host ( Abd et al, 2003 ; Mahajan et al, 2011 ; Ozanic et al, 2015 ) – a niche inhabited with a lower abundance of antibiotic-producing microbes.…”

Section: Discussionmentioning

confidence: 98%

Temperature-Dependent Gentamicin Resistance of Francisella tularensis is Mediated by Uptake Modulation

et al. 2016

View full text Add to dashboard Cite

Gentamicin (Gm) is an aminoglycoside commonly used to treat bacterial infections such as tularemia – the disease caused by Francisella tularensis. In addition to being pathogenic, F. tularensis is found in environmental niches such as soil where this bacterium likely encounters Gm producers (Micromonospora sp.). Here we show that F. tularensis exhibits increased resistance to Gm at ambient temperature (26°C) compared to mammalian body temperature (37°C). To evaluate whether F. tularensis was less permeable to Gm at 26°C, a fluorescent marker [Texas Red (Tr)] was conjugated with Gm, yielding Tr-Gm. Bacteria incubated at 26°C showed reduced fluorescence compared to those at 37°C when exposed to Tr-Gm suggesting that uptake of Gm was reduced at 26°C. Unconjugated Gm competitively inhibited uptake of Tr-Gm, demonstrating that this fluorescent compound was taken up similarly to unconjugated Gm. Lysates of F. tularensis bacteria incubated with Gm at 37°C inhibited the growth of Escherichia coli significantly more than lysates from bacteria incubated at 26°C, further indicating reduced uptake at this lower temperature. Other facultative pathogens (Listeria monocytogenes and Klebsiella pneumoniae) exhibited increased resistance to Gm at 26°C suggesting that the results generated using F. tularensis may be generalizable to diverse bacteria. Regulation of the uptake of antibiotics provides a mechanism by which facultative pathogens survive alongside antibiotic-producing microbes in nature.

show abstract

Section: Discussionmentioning

confidence: 98%

Temperature-Dependent Gentamicin Resistance of Francisella tularensis is Mediated by Uptake Modulation

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Our results corroborate previous studies that have shown vigorous growth of F. novicida in hemocytes (Santic et al, 2009 ). Studies of F. novicida within arthropod cells identified similar molecular mechanisms of pathogenesis, i.e., intracellular trafficking, as in mammalian cells (Ozanic et al, 2015 ), but the species nevertheless utilizes different virulence factors for proliferation in mammal and arthropod cells (Read et al, 2008 ; Santic et al, 2009 ; Åhlund et al, 2010 ).…”

Section: Discussionmentioning

confidence: 99%

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

Thelaus

Lundmark

Lindgren

et al. 2018

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Francisella tularensis, a highly virulent bacteria that causes the zoonotic disease tularemia, is considered a potential agent of biological warfare and bioterrorism. Although the host range for several species within the Francisella is known, little is known about the natural reservoirs of various Francisella species. The lack of knowledge regarding the environmental fates of these pathogens greatly reduces the possibilities for microbial risk assessments. The greater wax moth (Galleria mellonella) is an insect of the order Lepidoptera that has been used as an alternative model to study microbial infection during recent years. The aim of this study was to evaluate G. mellonella as a model system for studies of human pathogenic and closely related opportunistic and non-pathogenic strains within the Francisella genus. The employed G. mellonella larvae model demonstrated differences in lethality between human pathogenic and human non-pathogenic or opportunistic Francisella species. The F. novicida, F. hispaniensis and F. philomiragia strains were significantly more virulent in the G. mellonella model than the strains of human pathogens F. t. holarctica and F. t. tularensis. Our data show that G. mellonella is a possible in vivo model of insect immunity for studies of both opportunistic and virulent lineages of Francisella spp., that produces inverse results regarding lethality in G. mellonella and incapacitating disease in humans. The results provide insight into the potential host specificity of F. tularensis and closely related members of the same genus, thus increasing our present understanding of Francisella spp. ecology.

show abstract

“…In S. enterica serovar Typhimurium, virulence factors [i.e., waaL responsible for ligation of O-antigen to LPS, invA and ssaD essential structural components of type 3 secretion systems (T3SS), clpV chaperone essential for protein secretion by type VI secretion systems (T6SS), and PhoP/PhoQ two-component system] were shown to be involved in intracellular survival in D. discoideum ( Riquelme et al, 2016 ). Interestingly, F. tularensis , the causal agent of tularemia, exhibits different survival mechanisms in macrophage and amoebae ( Ozanic et al, 2015 ). In macrophages, F. tularensis escapes from acidified phagosomes to the cytosol and then proliferates, while in H. vermiformis , it replicates in non-acidified phagosomes ( Santic et al, 2011 ).…”

Section: Intracellular Pathogensmentioning

confidence: 99%

Dual Role of Mechanisms Involved in Resistance to Predation by Protozoa and Virulence to Humans

2018

View full text Add to dashboard Cite

Most opportunistic pathogens transit in the environment between hosts and the environment plays a significant role in the evolution of protective traits. The coincidental evolution hypothesis suggests that virulence factors arose as a response to other selective pressures rather for virulence per se. This idea is strongly supported by the elucidation of bacterial-protozoal interactions. In response to protozoan predation, bacteria have evolved various defensive mechanisms which may also function as virulence factors. In this review, we summarize the dual role of factors involved in both grazing resistance and human pathogenesis, and compare the traits using model intracellular and extracellular pathogens. Intracellular pathogens rely on active invasion, blocking of the phagosome and lysosome fusion and resistance to phagocytic digestion to successfully invade host cells. In contrast, extracellular pathogens utilize toxin secretion and biofilm formation to avoid internalization by phagocytes. The complexity and diversity of bacterial virulence factors whose evolution is driven by protozoan predation, highlights the importance of protozoa in evolution of opportunistic pathogens.

show abstract

The Divergent Intracellular Lifestyle of Francisella tularensis in Evolutionarily Distinct Host Cells

Cited by 35 publications

References 38 publications

Temperature-Dependent Gentamicin Resistance of Francisella tularensis is Mediated by Uptake Modulation

Temperature-Dependent Gentamicin Resistance of Francisella tularensis is Mediated by Uptake Modulation

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

Dual Role of Mechanisms Involved in Resistance to Predation by Protozoa and Virulence to Humans

Contact Info

Product

Resources

About