Current mainstream antibiotics are derivatives extracted from microbes or use the basic structures of known classes to chemically form synthetic drugs. Unfortunately, as resistance amongst pathogens increases they becoming redundant. Nature may provide a new source of antimicrobials which could help fight against multidrug- resistant pathogens.
4.1.
Phytochemicals their structure, function and clinical
uses.
Many of the drugs we use today; from cancer drugs such as Taxol to painkillers, were found through the analysis of plant-based compounds. Plants are subject to
pathogenic attack; in response to this threat they produce antimicrobials. There is a potential therefore for some of these compounds to be ideal replacements for conventional antibiotics. (Mann 2002; Trang et al. 2015).
Extracts taken from the Helichrysum italicum, Hieracium pilosella, Lonicera
caprifolium demonstrated inhibitory activity during the disc diffusion tests averaging 10mm zones of clearance. The extracts were effective against strains of aerobes and anaerobes including E. coli and S. aureus. Analysis of the extracts via
chromatography found the active compounds to be alkaloids, flavonoids and terpenes. This shows the potential of phytochemicals being utilised as clinical antimicrobials (Nostro et al. 2000).
4.1.1. Lichen derived antimicrobial
Usnic acid is a lichen metabolite with strong antimicrobial properties. Usnic acid inhibited gram-positive bacteria, even at low concentrations; it was highly effective against B. subtillis and S. aureus (Lauterwein et al. 1995).
Usnic acid showed no inhibitory effects against E. coli but at higher concentrations was shown to have an inhibitory effect against V. harveyi, a gram-negative
bacterium. The results also suggest the potential of E. coli having a certain amount of resistance to the compound, showing a potential for other bacteria to also develop resistance (Maciazg-Dorszynska et al. 2014).
4.2. Insect immune defence against environmental
bacteria.
Many insects inhabit environments with high bacterial density; many of these bacteria are pathogenic and potentially harmful to the insects yet the insects can resist the bacteria and effectively fight infections. This would be impossible without defences protecting them from the bacteria. By researching and studying these defences we may be able to synthesise novel antimicrobials to help fight against multidrug resistance and have a greater appreciation for the mechanisms developed by insects (Gross et al. 2008).
4.2.1. Rove beetle antimicrobials
Rove beetle naturally live in detritus and decaying leaf matter, therefore could be a potential source of antimicrobials. Researchers found the beetles produce stenusine, an alkaloid compound that covers their entire body. In tests with stenusine and norstenusine against bacterial strains, a broad spectrum antimicrobial effect was
4.2.2. Carrion beetle antimicrobial secretions
Carrion beetle larvae live and develop in decaying carcases of animals, thus are exposed to very high levels of pathogenic bacteria as are their offspring. The beetles secrete antimicrobial compounds onto offspring to protect them from infection. This shows parents transferring compounds to their young. When tested, the secretions showed no effect against E. coli, but it was effective against B. subtilis. The
compounds do not damage the cell wall structures but do possess lytic activity (Arce et al. 2013).
4.2.3. Larval antifungal
Salicylaldehyde secretions of Chrysomela larvae revealed that they act against both E. coli prokaryotic cells and fungal eukaryotic cells. The salicylaldehyde proves that there are simple non-peptidyl antimicrobials which are highly effective against a range of pathogens; a compound with broad activity would be very effective for general usage (Gross et al. 2002).
4.2.4. Bee honey and royal jelly
In modern medicine honey is used to treat wounds; the application of Manuka honey is now commonplace within hospitals for general wound care and preventing
infection. This not only reduces dependency on antibiotics but lowers risk of adverse side effects (Mandal and Mandal 2011).
Much of the antimicrobial effect associated with honey is due to the enzymatic production of hydrogen peroxide. Manuka honey is different; it displays significant antibacterial effects even when the hydrogen peroxide activity is blocked. It has been thought that this is due to the low pH and high sugar content making bacterial growth very difficult. Manuka honey has been shown to be effective against
antibiotic-resistant bacterial strains, further adding to its potential as a therapeutic solution to topical antibiotics (Willix et al 1992; Hillitt et al. 2016).
Royal jelly too has been shown to possess antimicrobial properties, due to the presence of 10-HDA (10-hydroxy-2-decenoic acid). Other similar small compounds may be present both within bees as well as other insect species which could be developed into antimicrobial drugs (Blue et al. 1959).
4.2.5. Ant egg antimicrobial protection.
Ants queens coat their eggs in a pheromonic antimicrobial secretion, using their singer as an antimicrobial delivery mechanism using it to coat the eggs as they are laid. Chromatographic analysis of the antimicrobial secretion has found that it is composed of alkaloids. The antimicrobial secretion is particularly effective against fungal pathogens. Unfortunately, the study did not describe the structure of the antimicrobial (Vandermeer and Morel 1995).
Female medflies actively secrete antimicrobial compounds to coat their eggs, protecting them from bacterial attack. The secretions were found to contain various AMPs these being two b-N-acetyl hexosaminidases and ceratotoxins A, B and C.
A minimum of 3 eggs was needed to form a clearance halo on bacterial plates against E. coli; increasing the number of eggs increases the clearance zone. As the active agent is a peptide it would have a limited clinical use, however this shows that some insects provide additional antimicrobial protection further study of these compounds may yield an effective molecule which may have potential clinical applications (Marchini et al. 1997).
4.2.7. African cattle tick egg antimicrobials
African cattle tick eggs have a strong antimicrobial presence, however unlike the previous examples the antimicrobial is incorporated into the egg wax. The ticks lay their eggs on the ground where they are vulnerable to pathogenic attack. Once extracted, the wax was found to inhibit E. coli, S. marcescens and B. subtilis, demonstrating activity against both gram positive and gram negative bacterial strains. Analysis of the wax found it was heat stable at 100oC and resistant to proteinase K and pronase, which are known for denaturing AMPs, . This suggests that the antimicrobial component of the wax is not a peptide. Although this shows the potential for insects to protect their offspring with non-AMP compounds the researchers were unable to further deduce the identity of the antimicrobial (Arrieta et al. 2006).
Millipedes have been found to produce antimicrobial secretions. Unlike in most other insects these are not AMPs but instead quinolones and esters of long chain fatty acids. Pachyiulus hungaricus was found to produce 44 of these antimicrobial compounds however the ratios of each varied between the sexes showing a level of sexual dimorphism with regards to the amount of quinolone to non-quinolone immune secretions.
The secretions were effective against both gram-positive and gram-negative strain as well as fungal pathogens. The secretions were tested against species such as
Staphylococcus epidermidis, Candida albicans and Cryptococcus neoformans. Gram-negative strains were less susceptible to the secretions, thought to be due to their cell wall makeup preventing the compounds from entering the cell. Fungi were found to be the most susceptible. The antifungal activity of the extract was found to be 10x more potent than commercial antifungal fluconazole. This further highlights the potential for insects to provide a viable alternative to many of the classic antibiotics but also a variability in the composition of the secretions between males and females of the same species (Stanković et al. 2016).