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Ixodes scapularis is a blood-feeding obligate ectoparasite responsible for transmitting the Lyme disease (LD) agent, Borrelia burgdorferi. During the feeding process, I. scapularis injects B. burgdorferi into the host along with its saliva, facilitating the transmission and colonization of the LD agent. Tick calreticulin (CRT) is one of the earliest tick saliva proteins identified and is currently utilized as a biomarker for tick bites. Our recent findings revealed elevated levels of CRT in the saliva proteome of B. burgdorferi-infected I. scapularis nymphs compared to uninfected ticks. Differential precipitation of proteins (DiffPOP) and LC-MS/MS analyses were used to identify the interactions between Ixs (I. scapularis) CRT and human plasma proteins and further explore its potential role in shielding B. burgdorferi from complement killing. We observed that although yeast-expressed recombinant (r) IxsCRT binds to the C1 complex (C1q, C1r, and C1s), the activator of complement via the classical cascade, it did not inhibit the deposition of the membrane attack complex (MAC) via the classical pathway. Intriguingly, rIxsCRT binds intermediate complement proteins (C3, C5, and C9) and reduces MAC deposition through the lectin pathway. Despite the inhibition of MAC deposition in the lectin pathway, rIxsCRT did not protect a serum-sensitive B. burgdorferi strain (B314/pBBE22Luc) from complement-induced killing. As B. burgdorferi establishes a local dermal infection before disseminating to secondary organs, it is noteworthy that rIxsCRT promotes the replication of B. burgdorferi in culture. We hypothesize that rIxsCRT may contribute to the transmission and/or host colonization of B. burgdorferi by acting as a decoy activator of complement and by fostering B. burgdorferi replication at the transmission site. [ABSTRACT FROM AUTHOR]

Background: Infections caused by Mycobacterium and pathogenic fungi have risen drastically over the past few decades. Moreover, with the increase in the number of immunocompromised (burn, organ transplant, chemotherapy, HIV) patients, these bacterial and fungal infections have led to alarming mortality rates. The drugs currently in use have become relatively ineffective due to ever increasing phenomenon of multidrug resistance. Furthermore, these drugs suffer with severe toxicity effects and also lack cost effectiveness., Objective: Under such compelling circumstances, it is pertinent to find novel and safer drugs with improved properties. One strategy that could be adopted is to identify natural bioactive compounds having antimicrobial potential with minimal side effects. Alternatively, drugs synthesized with the help of combinatorial chemistry leading to enhanced antimicrobial properties could be another strategy., Result: This article summarizes at a common platform the current scenario of the available natural as well as synthetic drugs targeting cell envelope that have patentable therapeutic interventions against predominant human bacterial and fungal pathogens.