Prediction of Novel Drug Targets and Vaccine Candidates against Human Lice (Insecta), Acari (Arachnida), and Their Associated Pathogens

Abstract

The emergence of drug-resistant lice, acari, and their associated pathogens (APs) is associated with economic losses; thus, it is essential to find new appropriate therapeutic approaches. In the present study, a subtractive proteomics approach was used to predict suitable therapeutics against these vectors and their infectious agents. We found 9701 proteins in the lice (Pediculus humanus var. corporis) and acari (Ixodes scapularis, Leptotrombidium deliense), and 4822 proteins in the proteomes of their APs (Babesia microti, Borreliella mayonii, Borrelia miyamotoi, Borrelia recurrentis, Rickettsia prowazekii, Orientia tsutsugamushi str. Boryong) that were non-homologous to host proteins. Among these non-homologous proteins, 365 proteins of lice and acari, and 630 proteins of APs, were predicted as essential proteins. Twelve unique essential proteins were predicted to be involved in four unique metabolic pathways of lice and acari, and 103 unique proteins were found to be involved in 75 unique metabolic pathways of APs. The sub cellular localization analysis of 115 unique essential proteins of lice and acari and their APs revealed that 61 proteins were cytoplasmic, 42 as membrane-bound proteins and 12 proteins with multiple localization. The druggability analysis of the identified 73 cytoplasmic and multiple localization essential proteins revealed 22 druggable targets and 51 novel drug targets that participate in unique pathways of lice and acari and their APs. Further, the predicted 42 membrane bound proteins could be potential vaccine candidates. Screening of useful inhibitors against these novel targets may result in finding novel compounds efficient for the control of these parasites.

Human pediculosis, a global public health problem

“…Challenges associated with the control of resistant lice highlight the need for more in depth understanding of the mechanisms of insecticide resistance, which may also lead to identification of new targets for the development and/or optimization of more effective compounds [ 115 , 133 ]. Recent advances in omics (genomics, transcriptomics, proteomics, and metabolomics) technologies can enable detailed characterization of any biological system at an unprecedented level and can therefore facilitate the understanding of the mechanism (s) that drive resistance of lice to insecticides.…”

In silico identification of drug targets and vaccine candidates against Bartonella quintana: a subtractive proteomics approach

“…Screening of non-host homologous proteins - To eliminate paralogs or duplicates from the B. quintana proteome, a 60% sequence identity threshold was applied using Cluster Database at High Identity with Tolerance (CD-HIT) 27 , 35 before further analysis. The resulting protein set was then subjected to BLASTp against the H. sapiens proteome, using an E-value cut-off of 10 -5 , as reported by Altschul et al 36 Only the protein sequences of B. quintana that exhibited no similarity with H. sapiens proteins were considered for subsequent analysis.…”

“… 19 , 20 , 21 , 22 , 23 One such approach is subtractive proteomics, an in silico method used to identify essential and non-host homologous proteins within a pathogen proteome. 18 , 24 , 25 , 26 , 27 By selecting essential proteins unique to pathogen survival and propagation, the subtractive proteomics approach allows the identification of novel drug targets and vaccine candidates within a pathogen, as shown for life-threatening pathogens such as Pseudomonas aeruginosa , 28 Streptococcus pneumonia 29 and Mycobacterium tuberculosis . 30 , 31 …”

Host Immune Responses to Salivary Components - A Critical Facet of Tick-Host Interactions

“…A complete sequence dataset of ticks is required to unravel the molecular mechanisms behind the differential expression and regulation of tick salivary proteins during feeding phases ( De Castro et al., 2017 ). The genomic and transcriptomic data of ticks, tick-borne pathogens, and pathogen’s infected tick can provide an aid in selection and characterization of the novel therapeutic targets and vaccine candidates ( Sette and Rappuoli, 2010 ; Antunes et al., 2012 ; Cramaro et al., 2015 ; De la Fuente and Contreras, 2015 ; Blecha et al., 2018 ; Davies et al., 2019 ; Ali et al., 2020a ; Ali et al., 2022 ; Jia et al., 2020 ). In recent years, a number of genomic and sialotranscriptome sequences have been annotated ( Hill and Wikel, 2005 ; Guerrero et al., 2006 ; Wang et al., 2007 ; Aljamali et al., 2009 ; Anatriello et al., 2010 ; Guerrero et al., 2010 ; Francischetti et al., 2011 ; Karim et al., 2011 ; Ribeiro et al., 2012 ; Schwarz et al., 2013 ; Garcia et al., 2014 ; Mudenda et al., 2014 ; Schwarz et al., 2014 ; Cramaro et al., 2015 ; Karim and Ribeiro, 2015 ; Xu et al., 2015 ; Yu et al., 2015 ; De Castro et al., 2016 ; De la Fuente et al., 2016 ; Gulia-Nuss et al., 2016 ; Barrero et al., 2017 ; De la Fuente et al., 2017 ; Maruyama et al., 2017 ; Ribeiro et al., 2017 ; Antunes et al., 2018 ; Miller et al., 2018 ; Nuss et al., 2018 ; Garcia et al., 2020 ; Jia et al., 2020 ; Couto et al., 2021 ; Oleaga et al., 2021b ).…”

“…Ixodid ticks are particularly different from Argasidae in the duration of their attachment to the host; they feed for several days depending on the life stage, as compared to soft ticks, which repeatedly feed for short periods of time ranging from minutes to hours ( Oliver, 1989 ; Sonenshine, 1991 ). Due to the prolonged feeding, hard ticks have developed myriad strategies; they create a feeding cavity by piercing the host skin through the chelicerae that induce a blood pool in the dermis, where ticks inoculate saliva to facilitate blood-feeding, and remain attached to the host ( Francischetti et al., 2009 ; Šimo et al., 2017 ; Boulanger and Wikel, 2021 ; Pham et al., 2021 ; Tirloni et al., 2021 ; Ali et al., 2022 ). These pharmacologically active molecules maintain the blood-feeding cavity and suppress the host defense mechanisms at the bite site ( Nuttall and Labuda, 2004 ; Francischetti et al., 2009 ; Ali et al., 2015a ; Martins et al., 2020 ).…”