By virtue of their antioxidant properties carotenoids could impart survival advantage for intracellular pathogens that are exposed to toxic levels of reactive oxygen species and reactive nitrogen species. The role of the carotenoids as virulence factor was first described in Staphylococcus aureus[1]. This pigment was demonstrated to function as an anti-oxidant inside neutrophils and protect the bacterium from the ROS [1]. A mutation in crtM gene, which is involved in biosyntheses of Staphyloxanthin [2] resulted in increased susceptibility to neutrophils' killing but this susceptibility could be rescued by inhibition of NADPH oxidase[1]. Furthermore, chemical inhibition of the pigment formation also resulted in decreased survival of the S. aureus in neutrophils and whole blood [1]. The role of carotenoids in virulence of the bacterial pathogen is further exemplified in Group B Streptococcus having hemolytic and cytolytic toxin. Interestingly, it was observed that the cylE gene enables bacteria of both the toxin production and the pigment production[3,4]. At low numbers, the Group B Streptococcus is ingested by neutrophils and macrophages wherein the pigment produced through the CylE is utilized as an antioxidant to protect the bacteria from ROS generated by the host cells and thus play an important role in intracellular survival of Streptococci[5] . Whereas, when bacteria can multiply in large numbers, the toxin encoded by the CylE leads to killing of the neutrophils and subversion of immune response [5]. Interestingly, a number of mycobacterial species also produce small amounts of carotenoids. Although, the role of carotenoids in TB pathogenesis is not known, however carotenoids play an important role in intracellular survival of the Mycobacterium marinum [6]. M. marinum is a fish/frog pathogen and is an excellent natural model of human tuberculosis. Transposon mutant strains of M. marinum were also found to be highly susceptible to killing by ROS, suggesting that carotenoids could neutralize macrophage cell mediated ROS[6]. Interestingly, these defects in M. marinum could be complemented by homologues carotenoid synthesis genes of M. tuberculosis further suggesting that carotenoid biosynthesis and virulence of M. tuberculosis are interrelated [6]. Additionally, pigmentation in mycobacteria is under the control of SigF[7] . SigF is an extracytoplasmic function (ECF) sigma factor of mycobacterium required for survival of heat shock, acidic pH and oxidative stress [8]. The carotenoids also play an important role in even in the phyto-pathogens. As an example, in Pantoea stewartii, carotenoids also play an important role in protection against the UV radiation and in neutralizing the ROS. Interestingly the pigmentation in this phytopathogen is regulated by virulence and quorum sensing regulator EsaI/EsaR. Besides these pathogens the carotenoids play an important role in biofilm formation of Cronobacter sakazakii[9]. C. sakazakii is an opportunistic food -borne pathogen that has been associated with infant and neonates’ infections arising due to the use of powdered infant formula. Carotenoids play an important role in prevention of phagocytosis of the C. sakazakii, since the crtY mutant is phagocytosed in much higher numbers compared to the wild type. Besides bacterial pathogens carotenoids play an important role in virulence of parasites affecting humans. Toxoplasma Gondii which causes fatal toxoplasmosis in immuno-compromised individuals is known to produces abscisic acid. Abscisic acid is derived from oxidation of carotenoid anthoxin. In T. Gondii, abscisic acid induces production of the second-messenger cyclic ADP ribose that could induce calcium signaling. Through the regulation of calcium signaling, abscisic acid plays an important role in modulation between lytic phase and chronic stage growth of T. Gondii and thus is central to its pathogenesis and transmission [10]. Furthermore, it helps in evasion of the parasite from the host cell. Inhibition of the carotenoid biosynthesis by fluridone results in delayed evasion of parasite and further induces development of the slow-growing, dormant cyst stage of the parasite [10]. Similar to T. gondii, Plasmodium falciparum, which cause malaria in humans also possess machinery to synthesize carotenoids. These carotenoids are synthesized during intraerythrocytic stages of P. falciparum [11]. Inhibition of carotenoids synthesis with chemical inhibitors results in inhibition of parasitic growth [11]. This inhibition could be reversed by providing exogenous lycopene suggesting that indeed carotenoid play an important role in parasitic growth [11]. below.
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