L. meyeri, L. wolbachii, L. idonii) and S2 (L. ilyithenensis,
L. kobayashii, L. ognonensis, L. ryugenii).
3 Leptospirosis and Virulence Factors
Pathogenic Leptospira species such as L. interrogans are the agents
of leptospirosis, which is a zoonotic disease responsible for more
than one million cases and 60,000 deaths per year worldwide
[9]. These are likely underestimates because of misdiagnosis and
underreporting, particularly in regions where other diseases with
similar nonspecific presentations, such as dengue and malaria, are
prevalent. Leptospirosis is also emerging due to global climate
changes resulting in more frequent and severe flooding events.
Although leptospirosis has high burden and mortality and is treatable, it is not acknowledged as a neglected tropical disease; thus,
efforts to raise awareness at the local and international levels are
needed [10].
Transmission to humans usually occurs through contact with
soils or surface waters contaminated with the urine of reservoir
animals such as rats that are asymptomatic carriers of the pathogens.
The severity of the disease appears to be mainly determined by the
interaction of the virulence characteristics of the infecting strain,
infecting inoculum size during environmental exposure, and host
susceptibility factors. However, the basic biology and virulence
factors of leptospires remain poorly characterized. This gap in our
knowledge is largely due to the fact that this research area has been
unattractive to both funders and researchers in the past decades
[10]. As a consequence, for example, genetic manipulation of
Leptospira remains relatively inefficient in comparison to other
bacteria [11].
Pathogenic Leptospira spp. have developed different strategies
such as rapid dissemination and ability to escape or hijack the host
immune system to successfully establish and maintain an infection.
The presence of endoflagella (or periplasmic flagella) enables the
pathogens to rapidly cross the mammalian cell barriers, disseminate
hematogenously, establish infection in target organs, and avoid
flagellin recognition from the innate immune system, thus enabling
the spirochetes to escape the immune attack during the infection
[11, 12]. Leptospires produce several adhesins for binding to several components of host cells, including the extracellular matrix
[13]. Under normal in vitro growth, the most abundant proteins
are the lipoproteins LipL32, LipL41, LipL36, and Loa22
[14]. These lipoproteins could potentially interact with host cells
and the immune system (complement, etc.) during the hematogenous dissemination of leptospires in the host. In addition, it has
been shown that the leptospiral LPS, in contrast to other
Leptospira and Leptospirosis
273
L. kobayashii, L. ognonensis, L. ryugenii).
3 Leptospirosis and Virulence Factors
Pathogenic Leptospira species such as L. interrogans are the agents
of leptospirosis, which is a zoonotic disease responsible for more
than one million cases and 60,000 deaths per year worldwide
[9]. These are likely underestimates because of misdiagnosis and
underreporting, particularly in regions where other diseases with
similar nonspecific presentations, such as dengue and malaria, are
prevalent. Leptospirosis is also emerging due to global climate
changes resulting in more frequent and severe flooding events.
Although leptospirosis has high burden and mortality and is treatable, it is not acknowledged as a neglected tropical disease; thus,
efforts to raise awareness at the local and international levels are
needed [10].
Transmission to humans usually occurs through contact with
soils or surface waters contaminated with the urine of reservoir
animals such as rats that are asymptomatic carriers of the pathogens.
The severity of the disease appears to be mainly determined by the
interaction of the virulence characteristics of the infecting strain,
infecting inoculum size during environmental exposure, and host
susceptibility factors. However, the basic biology and virulence
factors of leptospires remain poorly characterized. This gap in our
knowledge is largely due to the fact that this research area has been
unattractive to both funders and researchers in the past decades
[10]. As a consequence, for example, genetic manipulation of
Leptospira remains relatively inefficient in comparison to other
bacteria [11].
Pathogenic Leptospira spp. have developed different strategies
such as rapid dissemination and ability to escape or hijack the host
immune system to successfully establish and maintain an infection.
The presence of endoflagella (or periplasmic flagella) enables the
pathogens to rapidly cross the mammalian cell barriers, disseminate
hematogenously, establish infection in target organs, and avoid
flagellin recognition from the innate immune system, thus enabling
the spirochetes to escape the immune attack during the infection
[11, 12]. Leptospires produce several adhesins for binding to several components of host cells, including the extracellular matrix
[13]. Under normal in vitro growth, the most abundant proteins
are the lipoproteins LipL32, LipL41, LipL36, and Loa22
[14]. These lipoproteins could potentially interact with host cells
and the immune system (complement, etc.) during the hematogenous dissemination of leptospires in the host. In addition, it has
been shown that the leptospiral LPS, in contrast to other
Leptospira and Leptospirosis
273