J. Michael Conlon

Bio: J. Michael Conlon is an academic researcher from Ulster University. The author has contributed to research in topics: Antimicrobial peptides & Temporin. The author has an hindex of 51, co-authored 356 publications receiving 11461 citations. Previous affiliations of J. Michael Conlon include University of New South Wales & University of Rouen.

Cloning of the cDNA encoding the urotensin II precursor in frog and human reveals intense expression of the urotensin II gene in motoneurons of the spinal cord

Abstract: Urotensin II (UII) is a cyclic peptide initially isolated from the caudal neurosecretory system of teleost fish. Subsequently, UII has been characterized from a frog brain extract, indicating that a gene encoding a UII precursor is also present in the genome of a tetrapod. Here, we report the characterization of the cDNAs encoding frog and human UII precursors and the localization of the corresponding mRNAs. In both frog and human, the UII sequence is located at the C-terminal position of the precursor. Human UII is composed of only 11 amino acid residues, while fish and frog UII possess 12 and 13 amino acid residues, respectively. The cyclic region of UII, which is responsible for the biological activity of the peptide, has been fully conserved from fish to human. Northern blot and dot blot analysis revealed that UII precursor mRNAs are found predominantly in the frog and human spinal cord. In situ hybridization studies showed that the UII precursor gene is actively expressed in motoneurons. The present study demonstrates that UII, which has long been regarded as a peptide exclusively produced by the urophysis of teleost fish, is actually present in the brain of amphibians and mammals. The fact that evolutionary pressure has acted to conserve fully the biologically active sequence of UII suggests that the peptide may exert important physiological functions in humans.

Activity of antimicrobial skin peptides from ranid frogs against Batrachochytrium dendrobatidis, the chytrid fungus associated with global amphibian declines

Abstract: Accumulating evidence suggests that a chytrid fungus, Batrachochytrium dendrobatidis, is responsible for recent declines in amphibian populations in Australia, Central America, Europe, and North America. Because the chytrid infects the keratinized epithelium of the skin, we investigated the possible role of antimicrobial peptides produced in the skin as inhibitors of infection and growth. We show here that 10 peptides representing eight families of peptides derived from North American ranid frogs can effectively inhibit growth of this chytrid. The peptides are members of the ranatuerin-1, ranatuerin-2, esculentin-1, esculentin-2, brevinin-2, temporin, palustrin-3, and ranalexin families. All the tested peptides inhibit growth of mature fungal cells at concentrations above 25 microM, and some of them inhibit at concentrations as low as 2 microM. A comparison of the sensitivity of infectious zoospores with that of mature cells showed that the zoospores are inhibited at significantly lower concentrations of peptides. To determine whether cold temperature interferes with the inhibitory effects of these peptides, we tested their effectiveness at both 22 and 10 degrees C. Although the peptides inhibit at both temperatures, they appear to be more effective against zoospores at the lower temperature. These results suggest that the ranid frogs have, within their repertoire of antimicrobial substances, a number of skin peptides that should be a deterrent to chytrid infection. This may provide some natural resistance to infection, but if environmental factors inhibit the synthesis and release of the skin peptides, the pathogen could gain the advantage.

Antimicrobial peptide defenses against chytridiomycosis, an emerging infectious disease of amphibian populations

Abstract: Chytridiomycosis, an emerging infectious disease (EID) of the skin caused by the chytrid fungus, Batrachochytrium dendrobatidis, has been linked with continuing amphibian population declines in the western USA, Central America, Europe, Africa, and Australia. Genetic analysis suggests that B. dendrobatidis is a recently emerged pathogen. This article reviews the biology of this pathogenic chytrid and the evidence for chytridiomycosis as a cause of declines in amphibian populations worldwide. Data are presented to show that antimicrobial peptides, produced in granular glands of the skin and released in high concentrations into skin secretions, are highly effective in inhibiting growth of B. dendrobatidis in vitro and may provide limited protection for some species. Ongoing studies suggest a correlation between resistance to lethal infection by B. dendrobatidis and synthesis of antimicrobial peptides by the host amphibian, but further research is needed to define better the role of antimicrobial peptides in protection of amphibian populations and the effect of environmental factors upon antimicrobial peptide synthesis.

Peptides with antimicrobial activity from four different families isolated from the skins of the North American frogs Rana luteiventris, Rana berlandieri and Rana pipiens.

Abstract: The skins of frogs of the genus Rana synthesize a complex array of antimicrobial peptides that may be grouped into eight families on the basis of structural similarity. A total of 24 peptides with differential growth-inhibitory activity towards the Gram-positive bacterium Staphylococcus aureus, the Gram-negative bacterium Escherichia coli and the yeast Candida albicans were isolated from extracts of the skins of three closely related North American frogs, Rana luteiventris (spotted frog), Rana berlandieri (Rio Grande leopard frog) and Rana pipiens (Northern leopard frog). Structural characterization of the antimicrobial peptides demonstrated that they belonged to four of the known families: the brevinin-1 family, first identified in skin of the Asian frog Rana porosa brevipoda; the esculentin-2 family, first identified in the European frog Rana esculenta; the ranatuerin-2 family, first identified in the North American bullfrog Rana catesbeiana; and the temporin family, first identified in the European frog Rana temporaria. Peptides belonging to the brevinin-2, ranalexin, esculentin-1 and ranatuerin-1 families were not identified in the extracts. Despite the close phylogenetic relationship between the various species of Ranid frogs, the distribution and amino-acid sequences of the antimicrobial peptides produced by each species are highly variable and species-specific, suggesting that they may be valuable in taxonomic classification and molecular phylogenetic analysis.

Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria?

Abstract: Antimicrobial peptides are an abundant and diverse group of molecules that are produced by many tissues and cell types in a variety of invertebrate, plant and animal species. Their amino acid composition, amphipathicity, cationic charge and size allow them to attach to and insert into membrane bilayers to form pores by 'barrel-stave', 'carpet' or 'toroidal-pore' mechanisms. Although these models are helpful for defining mechanisms of antimicrobial peptide activity, their relevance to how peptides damage and kill microorganisms still need to be clarified. Recently, there has been speculation that transmembrane pore formation is not the only mechanism of microbial killing. In fact several observations suggest that translocated peptides can alter cytoplasmic membrane septum formation, inhibit cell-wall synthesis, inhibit nucleic-acid synthesis, inhibit protein synthesis or inhibit enzymatic activity. In this review the different models of antimicrobial-peptide-induced pore formation and cell killing are presented.

The Multifunctional Fish Gill: Dominant Site of Gas Exchange, Osmoregulation, Acid-Base Regulation, and Excretion of Nitrogenous Waste

Abstract: The fish gill is a multipurpose organ that, in addition to providing for aquatic gas exchange, plays dominant roles in osmotic and ionic regulation, acid-base regulation, and excretion of nitrogenous wastes Thus, despite the fact that all fish groups have functional kidneys, the gill epithelium is the site of many processes that are mediated by renal epithelia in terrestrial vertebrates Indeed, many of the pathways that mediate these processes in mammalian renal epithelial are expressed in the gill, and many of the extrinsic and intrinsic modulators of these processes are also found in fish endocrine tissues and the gill itself The basic patterns of gill physiology were outlined over a half century ago, but modern immunological and molecular techniques are bringing new insights into this complicated system Nevertheless, substantial questions about the evolution of these mechanisms and control remain

Peptide Antimicrobial Agents

Abstract: Antimicrobial host defense peptides are produced by all complex organisms as well as some microbes and have diverse and complex antimicrobial activities. Collectively these peptides demonstrate a broad range of antiviral and antibacterial activities and modes of action, and it is important to distinguish between direct microbicidal and indirect activities against such pathogens. The structural requirements of peptides for antiviral and antibacterial activities are evaluated in light of the diverse set of primary and secondary structures described for host defense peptides. Peptides with antifungal and antiparasitic activities are discussed in less detail, although the broad-spectrum activities of such peptides indicate that they are important host defense molecules. Knowledge regarding the relationship between peptide structure and function as well as their mechanism of action is being applied in the design of antimicrobial peptide variants as potential novel therapeutic agents.

BRIEF COMMUNICATION ARISING: Gut hormone PYY3-36 physiologically inhibits food intake

Abstract: Food intake is regulated by the hypothalamus, including the melanocortin and neuropeptide Y (NPY) systems in the arcuate nucleus. The NPY Y2 receptor (Y2R), a putative inhibitory presynaptic receptor, is highly expressed on NPY neurons in the arcuate nucleus, which is accessible to peripheral hormones. Peptide YY3-36 (PYY3-36), a Y2R agonist, is released from the gastrointestinal tract postprandially in proportion to the calorie content of a meal. Here we show that peripheral injection of PYY3-36 in rats inhibits food intake and reduces weight gain. PYY3-36 also inhibits food intake in mice but not in Y2r-null mice, which suggests that the anorectic effect requires the Y2R. Peripheral administration of PYY3-36 increases c-Fos immunoreactivity in the arcuate nucleus and decreases hypothalamic Npy messenger RNA. Intra-arcuate injection of PYY3-36 inhibits food intake. PYY3-36 also inhibits electrical activity of NPY nerve terminals, thus activating adjacent pro-opiomelanocortin (POMC) neurons. In humans, infusion of normal postprandial concentrations of PYY3-36 significantly decreases appetite and reduces food intake by 33% over 24 h. Thus, postprandial elevation of PYY3-36 may act through the arcuate nucleus Y2R to inhibit feeding in a gut–hypothalamic pathway.

Mode of action of membrane active antimicrobial peptides.

Abstract: Water-membrane soluble protein and peptide toxins are used in the defense and offense systems of all organisms, including plants and humans. A major group includes antimicrobial peptides, which serve as a nonspecific defense system that complements the highly specific cell-mediated immune response. The increasing resistance of bacteria to conventional antibiotics stimulated the isolation and characterization of many antimicrobial peptides for potential use as new target antibiotics. The finding of thousands of antimicrobial peptides with variable lengths and sequences, all of which are active at similar concentrations, suggests a general mechanism for killing bacteria rather than a specific mechanism that requires preferred active structures. Such a mechanism is in agreement with the “carpet model” that does not require any specific structure or sequence. It seems that when there is an appropriate balance between hydrophobicity and a net positive charge the peptides are active on bacteria. However, selective activity depends also on other parameters, such as the volume of the molecule, its structure, and its oligomeric state in solution and membranes. Further, although many studies support that bacterial membrane damage is a lethal event for bacteria, other studies point to a multihit mechanism in which the peptide binds to several targets in the cytoplasmic region of the bacteria.