Bovine hemoglobin: An attractive source of antibacterial peptides

Nedjar‐Arroume, Naïma; Dubois-Delval, Véronique; Adjé, Estelle Yaba; Traisnel, Jonathan; Krier, François; Mary, P.; Kouach, Mostafa; Briand, Gilbert; Guillochon, Didier

doi:10.1016/j.peptides.2008.01.011

Cited by 120 publications

(144 citation statements)

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“…1). Some hemoglobin peptides from bovines and humans are active against bacteria (22,23). Therefore, the observed high level of sequence similarity may be important for understanding the antimicrobial activity of hemoglobin or its segments (24).…”

Section: Sequence Characteristicsmentioning

confidence: 99%

Potential of Novel Antimicrobial Peptide P3 from Bovine Erythrocytes and Its Analogs To Disrupt Bacterial Membranes In Vitro and Display Activity against Drug-Resistant Bacteria in a Mouse Model

Zhang

Wang

et al. 2015

Antimicrob Agents Chemother

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With the emergence of many antibiotic-resistant strains worldwide, antimicrobial peptides (AMPs) are being evaluated as promising alternatives to conventional antibiotics. P3, a novel hemoglobin peptide derived from bovine erythrocytes, exhibited modest antimicrobial activity in vitro. We evaluated the antimicrobial activities of P3 and an analog, JH-3, both in vitro and in vivo. The MICs of P3 and JH-3 ranged from 3.125 g/ml to 50 g/ml when a wide spectrum of bacteria was tested, including multidrug-resistant strains. P3 killed bacteria within 30 min by disrupting the bacterial cytoplasmic membrane and disturbing the intracellular calcium balance. Circular dichroism (CD) spectrometry showed that P3 assumed an ␣-helical conformation in bacterial lipid membranes, which was indispensable for antimicrobial activity. Importantly, the 50% lethal dose (LD 50 ) of JH-3 was 180 mg/kg of mouse body weight after intraperitoneal (i.p.) injection, and no death was observed at any dose up to 240 mg/kg body weight following subcutaneous (s.c.) injection. Furthermore, JH-3 significantly decreased the bacterial count and rescued infected mice in a model of mouse bacteremia. In conclusion, P3 and an analog exhibited potent antimicrobial activities and relatively low toxicities in a mouse model, indicating that they may be useful for treating infections caused by drug-resistant bacteria.T he overuse of traditional antibiotics has triggered the frequent emergence of multidrug-resistant (MDR) bacteria, which pose significant threats to public health. Bacterial resistance is usually attributable to mutations and can spread, rendering the problem worse (1-3). Extensively mutated bacteria become resistant to many conventional chemotherapeutics. Since the early 1960s, many novel antibiotics have been prepared, but these are usually chemical variations of older and conventional antibiotics (4). There is an urgent need to find novel antimicrobial agents that control infections caused by MDR bacteria.Antimicrobial peptides (AMPs) have recently attracted significant attention (5). They are primitive components of innate immune systems and play multiple roles in immune defense (6, 7). AMPs are widespread in unicellular organisms, plants, and animals, and more than 1,600 have been identified in a wide range of organisms (8-10). Most natural AMPs exhibit broad-spectrum activities against bacteria (including MDR bacteria), fungi, viruses (including HIV), and tumors (11-13). Although many potent AMPs have been identified, a lack of knowledge about the mechanisms of action and high-level AMP toxicities are major obstacles on the path to clinical use (14). Therefore, the design of novel potent AMPs exhibiting low toxicities in vivo and the identification of the mechanisms of AMP-membrane interactions are important for the development of novel antimicrobial agents.Recently, we reported the first isolation of P3, a component of the bovine hemoglobin ␣-subunit (15). Its primary sequence is VNFKLLSHSLLVTLASHL (1,992.401 Da). The bovine hemoglobin P3 ...

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Section: Sequence Characteristicsmentioning

confidence: 99%

Potential of Novel Antimicrobial Peptide P3 from Bovine Erythrocytes and Its Analogs To Disrupt Bacterial Membranes In Vitro and Display Activity against Drug-Resistant Bacteria in a Mouse Model

Zhang

Wang

et al. 2015

Antimicrob Agents Chemother

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“…Studies have shown that the respiratory protein hemoglobin can produce ROS (Jiang et al, 2007). Recently, studies have also shown that antibacterial peptides derived from hemoglobins and intact hemoglobins have antibacterial activity in some higher vertebrates (Parish et al, 2001;Nedjar-Arroume et al, 2008). Studies have also demonstrated that hemoglobin is able to detect, scavenge, and detoxify NO; NO detoxification has been linked to bacterial resistance (Gardner and Gardner, 2002;Wajcman et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

“…In addition to supporting aerobic metabolism by providing O 2 , hemoglobins fulfill a broad range of other functions including O 2 sensing, detoxification of harmful reactive oxygen species (ROS), signaling in oxygen-dependent metabolic pathways, and production and elimination of NO (Terwilliger, 1998;Wajcman et al, 2009;Ebner et al, 2010). Hemoglobin (Hb) is also a source of antibacterial peptides in many animals; intact hemoglobin and its fractions exhibit antimicrobial activity against Gram-positive and -negative bacteria (Parish et al, 2001;Nedjar-Arroume et al, 2008). Human Hb can induce oxidative stress that may contribute to MMP-9 activation and BBB dysfunction, leading to apoptosis in vivo (Katsu et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Structure and immune expression analysis of hemoglobin genes from the blood clam Tegillarca granosa

Bao

Wang²,

Zhang³

2013

Genet. Mol. Res.

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ABSTRACT. Hemoglobin (Hb) is the major protein component of erythrocytes in animals with red blood, although it can serve additional functions beyond the transport of oxygen. The blood clam (Tegillarca granosa) is one of the few mollusks that has Hb, although the structure and function of molluskan Hbs remain unclear. We characterized two unique and highly compartmentalized blood clam hemoglobin genes, Tg-HbIIA and Tg-HbIIB, at the molecular level. The full-length cDNA of Tg-HbIIA was 731 bp with a 450-bp open reading frame encoding 150 amino acids; that of Tg-HbIIB was 698 bp, with a 456-bp open reading frame encoding 152 amino acids. Their intronic regions were amplified by PCR. The two genes showed the typical 2 intron/3 exon organization found in T. granosa. The 3-D structures of the three blood clam Tg-Hbs were predicted using the SWISS-MODEL Protein Modeling Server, and a phylogenetic analysis was conducted to investigate its evolution. As quantified by qRT-PCR, the expression levels of Tg-HbIIA and Tg-HbIIB were significantly upregulated upon challenge by Vibrio

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“…Adicionalmente, verificou-se que as subunidades α e β da hemoglobina de diversos vertebrados apresentam atividade contra bactérias Gram-positivas, Gram-negativas e fungos (Parish et al, 2001) e, nos últimos 10 anos, vários trabalhos têm descrito a atividade antimicrobiana de peptídeos derivados da hidrólise química ou enzimática de hemeproteínas (Froidevaux et al, 2001;Liepke et al, 2003;Mak et al, 2004;Daoud et al, 2005;Nedjar-Arroume et al, 2006;Nedjar-Arroume et al, 2008). Tais peptídeos an-timicrobianos passaram a ser coletivamente denominados hemocidinas (Mak et al, 2000).…”

Section: Hemoglobina Como Fonte De Peptídeos Bioativosunclassified

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2011

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RevisãoRevista da Biologia (2010) 6b: 1-6 2 Contato do autor:almenara@usp.br Recebido 19out10 Aceito 10mar11 PublicadoResumo. Nematóides entomopatogênicos são aqueles capazes de matar insetos. Essa propriedade inseticida é decorrente de um tipo bastante peculiar de simbiose estabelecida entre o verme e uma bactéria, sendo este último organismo o responsável pela morte do inseto em si. Além de oferecer dados interessantes para a compreensão biológica dos mecanismos envolvidos na manutenção de uma simbiose, os nematóides entomopatogênicos representam uma ferramenta potencial para controle de insetos-pragas da agricultura e até mesmo de aracnídeos, como carrapatos. Adicionalmente, o estudo de bactérias entomopatogênicas vem permitindo a identificação de diferentes compostos bioativos de origem microbiana. Palavras-chave. Entomopatogênico; nematóide; simbiose; Photorhabdus; Heterorhabditis.Abstract. Entomopathogenic nematodes are those capable of killing insects. This inseticide property is due to a rather peculiar kind of symbiosis established between the worm and bacteria, the latter being the main responsible for the death of the insect. Besides offering interesting data to understand the biological mechanisms involved in symbiosis, the entomopathogenic nematodes represent a potential tool to control insect pests in agriculture and even arachnids like ticks. Additionally, the study of entomopathogenic bacteria is leading to the identification of different bioactive compounds of microbial origin. Keywords Revisão Nematoides Entomopatogênicos (NEPs)Tradicionalmente, organismos parasitas são definidos como aqueles que vivem em associação com outro organismo (hospedeiro) do qual retiram meios para sua sobrevivência e reprodução, normalmente causando danos à saúde da espécie parasitada. É esta a definição encontrada, por exemplo, nos livros didáticos e nos dicionários. Parasitar, portanto, seria a simbiose (associação biológica) na qual um organismo vive junto de outro para tirar proveito, explorar. Por essa razão o termo é empregado não somente em Biologia, mas também pejorativamente, na língua portuguesa, para classificar as pessoas que não trabalham e vivem às custas de outras. Uma idéia bastante difundida é a de que um parasita eficiente seria aquele que causa pouco dano ao hospedeiro, numa forma de "preservar" seu ambiente de vida pelo máximo de tempo possível (Ebert & Herre, 1996). No entanto, estudos mais recentes questionam essa afirmação ao demonstrar uma crescente complexidade dentro deste há-bito de vida (ver a excelente discussão de Maynard-Smith, 1998). Uma questão fundamental no estudo da interação parasita-hospedeiro é a reconstrução da história deste tipo de associação ou, em termos mais biológicos, desta simbiose. É importante reunir dados na tentativa de definir se os parasitas e seus hospedeiros estão coevoluindo, ou seja, sofrendo alterações selecionadas em ambos os organismos durante toda a sua história evolutiva (a mudança de um acarreta mudanças no outro, e vice-versa) ou, alternativamente,...

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Bovine hemoglobin: An attractive source of antibacterial peptides

Cited by 120 publications

References 34 publications

Potential of Novel Antimicrobial Peptide P3 from Bovine Erythrocytes and Its Analogs To Disrupt Bacterial Membranes In Vitro and Display Activity against Drug-Resistant Bacteria in a Mouse Model

Potential of Novel Antimicrobial Peptide P3 from Bovine Erythrocytes and Its Analogs To Disrupt Bacterial Membranes In Vitro and Display Activity against Drug-Resistant Bacteria in a Mouse Model

Structure and immune expression analysis of hemoglobin genes from the blood clam Tegillarca granosa

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