scholarly journals The oxidative stress response and virulence of pathogenic Leptospira are controlled by the interplay of two peroxide stress regulators

2020 ◽  
Author(s):  
Crispin Zavala-Alvarado ◽  
Antony T. Vincent ◽  
Odile Sismeiro ◽  
Rachel Legendre ◽  
Hugo Varet ◽  
...  

AbstractPathogenic Leptospira are the causative agents of leptospirosis, the most widespread zoonotic infectious disease. Leptospirosis is a potentially severe and life-threatening emerging disease with highest burden in sub-tropical areas and impoverish populations. Mechanisms allowing pathogenic Leptospira to survive inside a host and induce acute leptospirosis are not fully understood. The ability to resist deadly oxidants produced by the host during infection is pivotal for Leptospira virulence. We have previously shown that genes encoding defenses against oxidants in L. interrogans are repressed by PerRA (encoded by LIMLP_10155), a peroxide stress regulator of the Fur family. In this study, we describe the identification and characterization of another putative PerR-like regulator (LIMLP_05620) in L. interrogans. Protein sequence and phylogenetic analyses indicated that LIMLP_05620 displayed all the canonical PerR amino acid residues and is restricted to pathogenic Leptospira clades. We therefore named this PerR-like regulator PerRB. In L. interrogans, the PerRB regulon is distinct from that of PerRA. While a perRA mutant had a greater tolerance to peroxide, inactivating perRB led to a higher tolerance to superoxide, suggesting that these two regulators have a distinct function in the adaptation of L. interrogans to oxidative stress. The concomitant inactivation of perRA and perRB resulted in a higher tolerance to both peroxide and superoxide and, unlike the single mutants, to the loss of Leptospira virulence. Interestingly, this correlated with major changes in gene and non-coding RNA expression, only observed in the double perRAperRB mutant. Notably, several virulence-associated genes (clpB, ligA/B, and lvrAB) were repressed. By obtaining the first double mutant in a pathogenic Leptospira strain, our study has uncovered for the first time the interplay of two PerRs, not only in the adaptation of Leptospira to oxidative stress, but also in their virulence and pathogenicity, most likely through the transcriptional control of a complex regulatory network.Author summaryLeptospirosis is a widespread infectious disease responsible for over one million of severe cases and 60 000 fatalities annually worldwide. This neglected and emerging disease has a worldwide distribution, but it mostly affects populations from developing countries in sub-tropical areas. The causative agents of leptospirosis are pathogenic bacterial Leptospira spp. There is a considerable deficit in our knowledge of these atypical bacteria, including their virulence mechanisms. In addition to the Leptospira PerRA regulator that represses defenses against peroxide, we have identified and characterized a second PerR regulator in pathogenic Leptospira species (PerRB) that participates in Leptospira tolerance to superoxide. Phenotypic and transcriptomic analyses of single PerRA and PerRB mutants suggest that the two PerRs fulfill distinct functions in the adaptation to oxidative stress. However, concomitant inactivation of PerRA and PerRB resulted in a higher tolerance to both peroxide and superoxide, but to a loss virulence.The absence of the two PerR regulators resulted in global and major changes in the transcriptional profile, including a dramatic decrease of several virulence factor expression. Our study has demonstrated that PerRA and PerRB cooperate to orchestrate a complex regulatory network involved in Leptospira virulence.

2021 ◽  
Vol 17 (12) ◽  
pp. e1009087 ◽  
Author(s):  
Crispin Zavala-Alvarado ◽  
Samuel G. Huete ◽  
Antony T. Vincent ◽  
Odile Sismeiro ◽  
Rachel Legendre ◽  
...  

Pathogenic Leptospira are the causative agents of leptospirosis, the most widespread zoonotic infectious disease. Leptospirosis is a potentially severe and life-threatening emerging disease with highest burden in sub-tropical areas and impoverished populations. Mechanisms allowing pathogenic Leptospira to survive inside a host and induce acute leptospirosis are not fully understood. The ability to resist deadly oxidants produced by the host during infection is pivotal for Leptospira virulence. We have previously shown that genes encoding defenses against oxidants in L. interrogans are repressed by PerRA (encoded by LIMLP_10155), a peroxide stress regulator of the Fur family. In this study, we describe the identification and characterization of another putative PerR-like regulator (LIMLP_05620) in L. interrogans. Protein sequence and phylogenetic analyses indicated that LIMLP_05620 displayed all the canonical PerR amino acid residues and is restricted to pathogenic Leptospira clades. We therefore named this PerR-like regulator PerRB. In L. interrogans, the PerRB regulon is distinct from that of PerRA. While a perRA mutant had a greater tolerance to peroxide, inactivating perRB led to a higher tolerance to superoxide, suggesting that these two regulators have a distinct function in the adaptation of L. interrogans to oxidative stress. The concomitant inactivation of perRA and perRB resulted in a higher tolerance to both peroxide and superoxide and, unlike the single mutants, a double perRAperRB mutant was avirulent. Interestingly, this correlated with major changes in gene and non-coding RNA expression. Notably, several virulence-associated genes (clpB, ligA/B, and lvrAB) were repressed. By obtaining a double mutant in a pathogenic Leptospira strain, our study has uncovered an interplay of two PerRs in the adaptation of Leptospira to oxidative stress with a putative role in virulence and pathogenicity, most likely through the transcriptional control of a complex regulatory network.


2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Tien-Huang Chen ◽  
Yi-Hsuan Chiang ◽  
Jiun-Nan Hou ◽  
Chih-Chieh Cheng ◽  
Eny Sofiyatun ◽  
...  

Dengue viruses (DENVs) cause dengue fever which is an important mosquito-borne disease in tropical areas. Generally, DENV does not cause cellular damage in mosquito cells. However, alterations in cytosolic calcium ions ([Ca2+]cyt) and the mitochondrial membrane potential (MMP), as well as accumulated reactive oxygen species (ROS), including superoxide anions (O2∙-) and hydrogen peroxide (H2O2), can be detected in C6/36 cells with DENV2 infection. Evident upregulation of BiP/GRP78 also appeared at 24 h postinfection in DENV2-infected C6/36 cells. As expression of BiP/GRP78 mRNA was reduced when the transcription factor X-box-binding protein-1 (XBP1) was knocked down in C6/36 cells, it demonstrated that BiP/GRP78 is the target gene regulated by the XBP1 signal pathway. We further demonstrated that the expression and splicing activity of XBP1 were upregulated in parallel with DENV2 infection in C6/36 cells. In C6/36 cells with BiP/GRP78 overexpression, oxidative stress indicators including [Ca2+]cyt, MMP,O2∙-, and H2O2were all pushed back to normal. Taken together, DENV2 activates XBP1 at earlier stage of infection, followed by upregulating BiP/GRP78 in mosquito cells. This regulatory pathway contributes a cascade in relation to oxidative stress alleviation. The finding provides insights into elucidating how mosquitoes can healthily serve as a vector of arboviruses in nature.


2020 ◽  
Author(s):  
◽  
Luke Spooner

Understanding the mountain pine beetle detoxification systems is vital for predicting its continued spread into the novel jack pine host. Phylogenetic analyses were conducted for mountain pine beetle catalase, glutathione peroxidase, superoxide dismutase, and peroxiredoxin. These proteins were generally conserved, but there were differences in some key functional motifs. Specifically, a peroxiredoxin (DPPrx1) contained a unique combination of hyperoxidation motifs. DPPrx1 and a superoxide dismutase (DPSOD1) were selected for further functional analyses and demonstrated higher reactivity when compared to other SOD and Prx proteins. Also, DPPrx1 experiences hyperoxidation at a lower H2O2 concentration (~0.06 mM) than human peroxiredoxin (~0.12 mM). In other systems, hyperoxidized peroxiredoxin does act as a signal molecule for the expression of other oxidative stress proteins. Therefore, due to its relatively high reactivity and potential role as a cellular signal, DPPrx1 could serve as a future pest management target.


2021 ◽  
Vol 2 (1) ◽  
pp. 21-29 ◽  
Author(s):  
Scott B. Halstead

When the underlying causes and mechanisms of emerging infectious disease problems are studied carefully, human behaviour is often involved. Even more often, the only methods of control or prevention available are to change human behaviour. Several major recent emerging disease problems can be cited. It is sometimes emphasized that it is human carelessness, human excesses, human ignorance or human habits of conquest or leisure which contribute directly to the biological niches that microorganisms are all too capable of exploiting. We must look at ourselves as the engines of microbial opportunism. It is not likely that we will ever conquer the microbial world;we must look instead to control the human factors that contribute to emergence.


2016 ◽  
Vol 5 (09) ◽  
pp. 1409 ◽  
Author(s):  
Shamsun Nahar ◽  
Jyotirmay Kalita ◽  
Lingaraj Sahoo ◽  
Bhaben Tanti*

Drought is a major abiotic stress that adversely affects the rice growth, mostly in the rainfed ecosystem that ultimately affects the biomass production and yield. Rice needs to adapt a series of physiological mechanisms with complicated regulatory network to fight and cope up with the unfavourable conditions due to drought stress. Morphological and physiological response in rice include inhibition of seed germination, slower growth rate, low root and shoot length, lower chlorophyll content, stomatal closure, lower rate of photosynthesis, yield reduction etc. Stress condition further results in development of response at the molecular level by the generation of reactive oxygen species (ROS) such as O2*-, H2O2, 1O2, OH* etc. which incites oxidative stress in the plants. Oxidative stress is overcome by the inherent capacity of plants to produce antioxidant species which may be enzymatic or non-enzymatic in nature. If however antioxidant defence mechanism cannot overpower the ROS generated, they cause oxidative damage to the plant tissues such as lipid peroxidation, protein oxidation, DNA damage, etc. resulting in cell death. Unlike other stresses, drought affects the physiology and biochemistry of the rice which adversely affects in the morphology and consequently delimits the yield of the plant. Therefore, understanding the morphological, biochemical and molecular mechanisms involved in rice against drought is utmost necessary for rice breeders to improve the rice for drought tolerant/resistance varieties for future green revolution. In this review, an attempt has been made to highlight the complex regulatory network involved in rice against drought with special emphasis on morphological, physiological and molecular mechanisms and to discuss the prospective and challenges for future plant breeders.


2020 ◽  
Vol 51 (5) ◽  
pp. 519-525
Author(s):  
Amel Ćutuk ◽  
Pamela Bejdić ◽  
Ermin Šaljić ◽  
Renata Lindtner Knific ◽  
Alenka Dovč ◽  
...  

Leptospirosis is an acute, subacute and chronical contagious disease of animals and humans. Causative agents of this disease belong to the genus Leptospira, family Leptospiraca. As a disease of wild animals, leptospirosis is widespread through Europe. Certain wild animals (rodents, fox and wild boars) are important reservoirs and highly probable vectors for the spread of infection into domestic animals and humans. During the hunting season, hunting dogs are often in direct or indirect contact with wild animals that could be carriers of this disease, and the possibility of appearance and spreading within this cohort of dogs is very high. The main reasons for this study on the prevalence of Leptospirosis in Bosnia and Herzegovina are the regular contact between hunting dogs and wild animals (carriers), and the lack of dataaboutLeptospirosisinhuntingdogs.In total, 175 serum samples from 15 towns of Bosnia and Herzegovina were tested. Twelve serovars of L. interrogans were used in the microscopic agglutination test. Presence of antibodies of four serovars was confirmed. Prevalence of seropositive dogs was 15.4% (27/175). Most positive dogs had a reaction to the Pomona serovar 51.8% (n=14), while the prevalence of the Sejroe serovar was 33.3%, Icterohaemorrhagiae serovar 11.1% and Bratislava serovar 3.7%. The highest number of positive reactions 55.5% (n=15) was with serum dilution of 1:200. This study showed that most infections in dogs were caused by serovars that are currently not included in commercial vaccines. One of the most efficient preventive measure could be vaccination with the serovars most often found in wild animals, as they appear to be the most common source of the infection.


2013 ◽  
Vol 58 (No. 10) ◽  
pp. 516-526 ◽  
Author(s):  
RVS Pawaiya ◽  
VK Gupta

Schmallenberg virus (SBV) infection is an emerging infectious disease of ruminants first described in Germany in November, 2011. Since then it has spread very rapidly to several European countries. The disease is characterised by fever, reduced milk production and diarrhoea in cattle and abortions, stillbirths and foetal abnormalities in sheep and goats. SBV is an enveloped, negative-sense, segmented, single-stranded RNA virus, classified in the genus Orthobunyavirus of the Bunyaviridae family, and is closely related to Akabane, Ainoa and Shamonda viruses. As of now there is no vaccine available for SBV, which poses a serious threat to naive ruminant population. Owing to its recent discovery, our understanding of Schmallenberg viral disease and its pathology and pathogenesis is limited. This article reviews the data reported so far on this emerging disease with regard to aetiology, epidemiology, pathogenesis, pathology, diagnosis and control and discusses the future scenario and implications of the disease.


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