Macin Family of Antimicrobial Proteins Combines Antimicrobial and Nerve Repair Activities

Jung, Sascha; Sönnichsen, Frank D.; Hung, Chien‐Wen; Tholey, Andreas; Boidin-Wichlacz, Céline; Haeusgen, Wiebke; Gelhaus, Christoph; Desel, Christine; Podschun, Rainer; Waetzig, Vicki; Tasiemski, Aurélie; Leippe, Matthias; Grötzinger, Joachim

doi:10.1074/jbc.m111.336495

Cited by 42 publications

(42 citation statements)

References 36 publications

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“…Mytimacins. Macins represent an emerging family of secreted, positively charged AMPs, relatively poorly studied but widespread in protostomes and combining antimicrobial and nerveerepair activities [163]. Five mussel macins (mytimacins) have been described so far in M. galloprovincialis [164], with the number of cysteines and disulfide bridges ranging from 8 (4 bridges) to 12 (6 bridges) ( Table 3).…”

Section: Mytimycinsmentioning

confidence: 99%

An updated molecular basis for mussel immunity

Gerdol

Venier

2015

Fish & Shellfish Immunology

134

163

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Non-self recognition with the consequent tolerance or immune reaction is a crucial process to succeed as living organisms. At the same time the interactions between host species and their microbiome, including potential pathogens and parasites, significantly contribute to animal life diversity. Marine filter-feeding bivalves, mussels in particular, can survive also in heavily anthropized coastal waters despite being constantly surrounded by microorganisms. Based on the first outline of the Mytilus galloprovincialis immunome dated 2011, the continuously growing transcript data and the recent release of a draft mussel genome, we explored the available sequence data and scientific literature to reinforce our knowledge on the main gene-encoded elements of the mussel immune responses, from the pathogen recognition to its clearance. We carefully investigated molecules specialized in the sensing and targeting of potential aggressors, expected to show greater molecular diversification, and outlined, whenever relevant, the interconnected cascades of the intracellular signal transduction. Aiming to explore the diversity of extracellular, membrane-bound and intracellular pattern recognition receptors in mussel, we updated a highly complex immune system, comprising molecules which are described here in detail for the first time (e.g. NOD-like receptors) or which had only been partially characterized in bivalves (e.g. RIG-like receptors). Overall, our comparative sequence analysis supported the identification of over 70 novel full-length immunity-related transcripts in M. galloprovincialis. Nevertheless, the multiplicity of gene functions relevant to immunity, the involvement of part of them in other vital processes, and also the lack of a refined mussel genome make this work still not-exhaustive and support the development of more specific studies.

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Section: Mytimycinsmentioning

confidence: 99%

An updated molecular basis for mussel immunity

Gerdol

Venier

2015

Fish & Shellfish Immunology

134

163

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“…Another macin family member, neuromacin, was also shown to aggregate bacteria and liposomes (6). The designated SWTK/R motif is also present in neuromacin, although it is not as prominent as in HM1.…”

Section: Discussionmentioning

confidence: 99%

“…The designated SWTK/R motif is also present in neuromacin, although it is not as prominent as in HM1. Nevertheless, both peptides show very similar molecular surface properties comprising two uncharged/hydrophobic hemispheres that sandwich a ring of cationic charges (6). Though the SWTK/R motif is well suited to explain the HM1-membrane interaction and subsequent aggregation in the case of neuromacin, the characteristic composition of the overall molecular surface of the peptide consequently must be partially complemented by alternative amino acid residues.…”

Section: Discussionmentioning

confidence: 99%

“…Peptides from this family lead to aggregation of bacteria, which originates from their striking molecular surface properties comprising two uncharged and hydrophobic hemispheres that sandwich a belt of positive charges (5,6). The corresponding mechanistic model was termed the barnacle model and was described for the first time for hydramacin-1 (HM1), the macin family founder (5).…”

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confidence: 99%

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Hydramacin-1 in Action: Scrutinizing the Barnacle Model

Michalek

Vincent

Podschun

et al. 2013

Antimicrob Agents Chemother

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c Hydramacin-1 (HM1) from the metazoan Hydra exerts antimicrobial activity against a wide range of bacterial strains. Notably, HM1 induces the aggregation of bacterial cells, accompanied by precipitation. To date, the proposed mechanism of peptide-lipid interaction, termed the barnacle model, has not been described on the molecular level. Here, we show by biochemical and biophysical techniques that the lipid-peptide interactions of HM1 are initiated by electrostatic and hydrophobic effects, in particular, by tryptophan and neighboring polar amino acid residues that cause an interfacial localization of the peptide between two self-contained lipid bilayers. The high binding constants of HM1 upon lipid interaction are in the range of other potent antimicrobial peptides, e.g., magainin, and can be reasonably explained by two distinct epitopes on the surface of the peptide's global structure, which both contain SWT(K/R) motifs. The residues of this motif favor localization of the peptide in the head group region of phospholipid bilayers up to a penetration depth of 4 Å and a minor participation of the lipids' hydrocarbon regions. Our results expand the knowledge about the molecular modes of action antimicrobial peptides use to tackle their target cells. Furthermore, the aggregation of living bacteria by HM1 was observed for a broad range of Gram-positive and Gram-negative bacteria. Therefore, the detailed view of peptide-lipid interactions described by the barnacle model consolidates it among the established models. Various antimicrobial peptides and proteins exert their antimicrobial activities by directly targeting the microbial membrane (1). Currently, only a few mechanistic models describe the peptides' modes of action in detail. Certain peptides form transient or stable membrane pores, as represented by the aggregate model, the toroidal-pore model, or the barrel stave model (2), or lead to micellization of membrane lipids, as specified by the carpet model (3). Furthermore, the peptides can translocate via the microbial membrane (aggregate model) and disturb essential intracellular processes. In addition, some antimicrobial peptides are reported to exert their modes of action more specifically, for example, by binding particular membrane compounds, such as lipid II, leading to inhibition of cell wall synthesis (4).Recently, members of a new antimicrobial protein family, the macins, were pronounced to exhibit a mode of action that clearly deviates from well-established mechanisms of membrane permeabilization. Peptides from this family lead to aggregation of bacteria, which originates from their striking molecular surface properties comprising two uncharged and hydrophobic hemispheres that sandwich a belt of positive charges (5, 6). The corresponding mechanistic model was termed the barnacle model and was described for the first time for hydramacin-1 (HM1), the macin family founder (5). It suggested a dual electrostatic, as well as hydrophobic, peptide-membrane interaction applied in parallel to two individual bact...

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“…Показано, что оральный ле-карственный препарат «Пиявит», разрешённый к клиническому применению с 1994 г., содержит все компоненты ССК МП, практически полно-стью сохраняющие свои активности при продол-жительном хранении [6]. «Пиявит», который го-товят, используя тела МП, содержит ткани и ме-таболиты последних, а также микроорганизмы микробиома МП и их биологически активные со-единения, часть которых способна проявлять ан-тимикробную активность [9,10]. Следовательно, качественный и количественный состав белков и других соединений в ССК и «Пиявите» суще-ственно различаются.…”

Section: журнал включен в перечень рецензируемых научных изданий вакunclassified

Sensitivity to natural antimicrobial complexes of mycoses incitants – representatives of gg. Candida and fusarium

Павлова¹,

Danyan²,

Chen³

et al. 2017

Zdor. obraz. XXI veke (Ž. naučn. statej)

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Шаньдунская академия сельскохозяйственных наук Китая, Цзинань, Китай. Аннотация. Различные микозы и заболевания, связанные с бактериально-грибными патогенами, представляют всё большую опасность из-за быстро распространяющихся устойчивости их возбудителей к используемым про-тивомикробным, в том числе -и противогрибковым средствам, иммунодефицита. Недавно доказано, что только комбинация нескольких антимикробных белков и/или пептидов (АМР) не вызывает возникновения резистентно-сти у патогенов. В связи с этим расширяются исследования антимикробной активности природных, эволюционно сбалансированных комплексов, содержащих АМР. Особое место среди таких комплексов занимает секрет слюн-ных клеток медицинской пиявки Hirudo medicinalis. В нашей работе установлено in vitro, что молодые гифы гриба Fusarium oxysporum и дрожжи Candida guillermondii чувствительны к антимикробному действию растворов сек-рета слюнных клеток медицинской пиявки, а также водного экстракта разрешённого к клиническому использо-ванию препарата «Пиявит», приготовленного на основе медицинской пиявки. Для изучения антифунгальной активности этих растворов использовали традиционные микробиологические методы, а также электронную мик-роскопию. Сделано предположение о вероятной перспективности (после дальнейших опытов, в том числе, in vivo) использования изучаемых природных антимикробных соединений, не вызывающих резистентности у мик-роорганизмов, в комплексном лечении микозов у пациентов с ослабленным иммунитетом, нарушениями функ-ционирования сердечно-сосудистой системы, печени, почек, и рядом других заболеваний -вместо традиционно используемых антибиотиков и некоторых других лекарств. Ключевые слова. секрет слюнных клеток медицинской пиявки Hirudo medicinalis (ССК МП); антимикробные белки и/или пептиды (АМР); природные комплексные противогрибковые средства -антимикотики. В последние годы различные микозы и забо-левания, обусловленные смесью бактериально-грибных патогенов, представляют всё большую опасность из-за быстро распространяющихся устойчивости их возбудителей к применяемым лекарствам, иммунодефицита, а также расшире-ния использования катетеризации, оперативных вмешательств [1, 2]. Эти факторы, наряду с до-статочно высокой токсичностью известных ан-тимикотиков, вызывающей множество нежела-тельных явлений при их применении, опреде-ляют не только актуальность поиска новых про-тивогрибковых средств, но и комплексную стра-тегию борьбы с микозами [3, 4]. При этом особое внимание стали уделять природным и искус-ственно созданным антимикробным пептидам (АМР), которые рассматривают, как альтерна-тиву традиционно используемым антибиотикам. Однако, часто препятствием для лечебного при-менения таких АМР является их высокая гемоли-тическая активность, а также токсичность для клеток пациентов [4]. Интенсивно изучают меха-низмы возникновения резистентности грибов к лекарственным препаратам и способы её преодо-

show abstract

Macin Family of Antimicrobial Proteins Combines Antimicrobial and Nerve Repair Activities

Cited by 42 publications

References 36 publications

An updated molecular basis for mussel immunity

An updated molecular basis for mussel immunity

Hydramacin-1 in Action: Scrutinizing the Barnacle Model

Sensitivity to natural antimicrobial complexes of mycoses incitants – representatives of gg. Candida and fusarium

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