Iranian Journal of Basic Medical Sciences ijbms.mums.ac.ir Cockroaches, locusts, and envenomating arthropods: a promising source of antimicrobials Mahnoor Ummul-Warah Faateemah Zehra Mosaheb 1, Naveed Ahmed Khan 1*, Ruqaiyyah Siddiqui 1 1 Department of Biological Sciences, School of Science and Technology, Sunway University, Selangor, Malaysia A R T I C L E I N F O A B S T R A C T Article type: Objective(s): To present a brief overview of various natural sources of antimicrobials with the aim Review article of highlighting invertebrates living in polluted environments as additional sources of antimicrobials. Materials and Methods: A PubMed search using antibacterials, antimicrobials, invertebrates, and Article history: natural products as keywords was carried out. In addition, we consulted conference proceedings, Received: Mar 9, 2018 Accepted: Jun 18, 2018 Results: Representative of a stupefying 95% of the fauna, invertebrates are fascinating organisms Keywords: whichoriginal have unpublished evolved strategiesresearch undertaken to survive ingerm-infested our laboratories, environments, and discussions yet they in specific have largely forums. been Antibacterial agents ignored. Since invertebrates such as cockroaches inhabit hazardous environments which are rampant Anti-infective agents with pathogens, they must have developed defense mechanisms to circumvent infections. This is Antimicrobial peptides corroborated by the presence of antimicrobial molecules in the nervous systems and hemolymph Communicable diseases of cockroaches. Antimicrobial compounds have also been unraveled from the nervous, adipose, and Drug resistance salivary glandular tissues of locusts. Interestingly, the venoms of arthropods including ants, scorpions, Invertebrate peptides and spiders harbor toxins, but also possess multiple antimicrobials. Conclusion: derived from a plentiful and diverse resource to combat fatal infectious diseases. Such antimicrobials from unusual These sources findings can potentially have rekindled be translated the hopes into for clinical newer practice, and enhanced however therapeutic intensive research agents is needed over the next several years to realize these expectations. ►Please cite this article as: Mosaheb MUWFZ, Khan NA, Siddiqui R. Cockroaches, locusts, and envenomating arthropods: a promising source of antimicrobials. Iran J Basic Med Sci 2018; 21:873-877. doi: 10.22038/IJBMS.2018.30442.7339 Introduction Ranked as the second leading killer, infectious properties (8). However, instead of focusing on an diseases pose a serious threat to humankind, accounting often been acclaimed for their beneficial antimicrobial for an estimated 17 million deaths (1). These statistics would be interesting to consider the fauna as well. Since comprise a daily toll of 50,000 men, women, and extinguishableinvertebrates represent antimicrobial a staggering source 95%from ofthe the flora, fauna it children dying, despite advances in antimicrobial (9) and have existed for millions of years in hazardous chemotherapy. Contrary to the wide belief that environments, they are promising candidates. These infectious diseases have been largely alleviated, malaria, creatures are believed to have developed antimicrobials to protect themselves from the pathogenic microbes threats, while HIV/AIDS, Ebola, dengue, and Zika pose (10). cholera,a major riskand totuberculosis human health alone (2, 3).remain For instance,significant in Some of the invertebrates thrive under hazardous 2015, 10.4 million cases with 1.4 million deaths have conditions known to humans. For instance, cockroaches been associated with tuberculosis alone (4). In part, this dwell in polluted environments, infested with multi- is attributed to the emergence of multi-drug resistant resistant pathogens. This led to the hypothesis that Mycobacterium tuberculosis, displaying resistance invertebrates possess antimicrobials as part of their against anti-tuberculosis drugs such as isoniazid and defense mechanisms (11). De facto, the innate immunity rifampicin (5). Antimicrobial resistance has engendered of invertebrates is highly responsive to bacterial a crisis amidst the soaring infection rates with stunted challenges, producing humoral antimicrobials as part antimicrobial discovery (6). The increase in multi-drug of its defense system (12). Furthermore, venoms of resistance of pathogens, hampered the progress of invertebrates including scorpions, spiders, and ants possess antimicrobial activity (13, 14). Thus, it is and temporal burden in devising new antimicrobial reasonable to explore invertebrates to recruit valuable antibioticchemotherapy. discovery, The bycurrently adding to availablethe existing antibiotics financial antimicrobial products of their defense mechanisms. encompass mainly structural analogs of antibiotics from Methods Hence, there is an urgent need to discover novel and A PubMed search using “antibacterials” and theeffective 1940-1980s antibiotics. era, often This with has sub-optimalsparked the efficacy antibiotic (7). “antimicrobials’ combined with “invertebrates” and hunt from natural sources. Plants and marine algae have “natural products” as keywords was carried out. In *Corresponding author: Naveed Ahmed Khan. Department of Biological Sciences, School of Science and Technology, Sunway University, Selangor, Malaysia. Tel: +60- 0374918622; Fax: +60-0356358630; Email: [email protected] Mosaheb et al. Invertebrates as source of antimicrobials addition, we consulted conference proceedings, original was determined (20). The effects were tested on S. unpublished research undertaken in our laboratories, epidermidis, S. aureus, and drug-resistant pathogens and discussions in forums (e.g., American Society for including methicillin-resistant S. aureus (MRSA) and Microbiology Annual Meeting in 2017, European Society pathogenic E. coli K1 (20). Bacteria incubated with of Clinical Microbiology and Infectious Diseases in 2017, PBS alone showed approx. 106 c.f.u. while bacteria the Free-Living Amoebae Meetings in 2017, and Spanish incubated with brain lysates showed zero colonies (20). Parasitology Society in 2017). In contrast, other tissue extracts such as fat bodies and muscles showed no effects and bacterial CFU were Results recovered in numbers similar to bacteria incubated with Locusts and cockroaches the solvent alone. The dose-dependent antibacterial Periplaneta americana cockroach (Linnaeus) is an L. migratoria retain their antibacterial properties at concentrations of humans in urbanized milieus (15). Cockroaches occupy assaysless than reflected 5 µg (12). that Furthermore, the brain lysates the high of bactericidal ancientpathogen-infested species of flying environments cockroaches and which thrive, coexist suggesting with property was retained even when the brain lysates were the presence of antibacterial molecules (11). In support, heated, but not when exposed to denaturing agents cockroach brain lysates exhibited potent bactericidal like SDS. Additionally, these antimicrobial peptides effects against methicillin-resistant Staphylococcus bear selective toxicity to both Gram-positive and aureus and pathogenic Escherichia coli K1 (11). Size- Gram-negative bacteria, without affecting eukaryotic exclusion analysis depicted low molecular-weight cells (20). In another study, immune-challenged L. compounds below 10 kDa were present in the brain migratoria were surveyed for antimicrobial activity extracts of P. americana. Furthermore, the brain lysates in the fat body lysates or salivary glands and palps depicted selective toxicity against pathogens but non- (19). The locusts were harnessed at the gregarious toxic to human cells, as analyzed through cytotoxicity phase during their metamorphosis and injected with assays on human brain microvascular endothelial cells Serratia marcescens, Nosema locustae, and Metarhizium (7). Preliminary studies unraveled novel neuropeptides anisopliae to stimulate the innate immunity and assess in the organ lysates (11). Smaller antimicrobial peptides the locust’s potential in antimicrobial production. arise from cleavage of these neuropeptides, notably Antibacterial assays against S. aureus and E. coli revealed from proenkephalin and prodermaseptin (12). These the antimicrobial activity of the lysates in the immune- comprise 24-34 subunit amphiphilic helical cysteine- challenged locusts. Reverse-transcription of the isolated free, 20-46 amino acid cysteine-rich, or 10-13 residue RNA indicated the up-regulated expression of 3 novel defensins in immune-challenged locusts including biologically-active compounds with useful therapeutic LmDEF-5, LmDEF-4, and both LmDEF-1 and LmDEF-3 lipophilic peptides. (16). The LC-MS identified many (19). Separation through PAGE yielded bands of 5 and hemolymph extracts revealed antimicrobial activity 11 kDa, representative of the small defensin peptides. effectagainst (7). a multitude The compounds of Gram-positive identified and from Gram-negative brain and Lv and colleagues successfully determined the presence bacteria, several viruses and fungi, and Candida albicans of three novel peptides as cysteine-rich defensins and (7). Moreover, isoquinoline and thiazine groups, another conserved defensin-like molecule (19). Thus, chromene-derived compounds, pyrrole-containing L. migratoria locusts harbor highly-evolved innate immunity to stimulate the production of antimicrobial peptides (19). entities, sulfonamides, furanones, and flavanones, which(7). Seraj protect and againstcolleagues inflammation,