Antimicrobial Peptides Versus Invasive Infections

Yeaman, Michael R.; Bayer, Arnold S.

doi:10.1007/3-540-29916-5_5

Cited by 26 publications

(20 citation statements)

References 99 publications

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“…This may reflect an enhanced susceptibility of the DAP r strains to neutrophil-based host defenses that are replete in the latter organs and accompany abscess formation. Alternatively, this reduced virulence may imply a defect in the seeding of distant target organs by the DAP r strain, i.e., a perturbation in hematogenous spread from vegetations to these distant organs by non-neutrophil-based mechanisms, such as the elaboration of platelet antimicrobial peptides within cardiac vegetations (34,35). Second, the apparent in vivo fitness defect of the DAP r strain could not be overcome by merely increasing the challenge inoculum from 10 6 to 10 7 CFU/ml.…”

Section: Discussionmentioning

confidence: 99%

Impact of High-Level Daptomycin Resistance in the Streptococcus mitis Group on Virulence and Survivability during Daptomycin Treatment in Experimental Infective Endocarditis

García-de-la-Mària

Xiong

Pericàs

et al. 2017

Antimicrob Agents Chemother

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Among the viridans group streptococci, the Streptococcus mitis group is the most common cause of infective endocarditis. These bacteria have a propensity to be ␤-lactam resistant, as well as to rapidly develop high-level and durable resistance to daptomycin (DAP). We compared a parental, daptomycin-susceptible (DAP s ) S. mitis/S. oralis strain and its daptomycin-resistant (DAP r ) variant in a model of experimental endocarditis in terms of (i) their relative fitness in multiple target organs in this model (vegetations, kidneys, spleen) when animals were challenged individually and in a coinfection strategy and (ii) their survivability during therapy with daptomycin-gentamicin (an in vitro combination synergistic against the parental strain). The DAP r variant was initially isolated from the cardiac vegetations of animals with experimental endocarditis caused by the parental DAP s strain following treatment with daptomycin. The parental strain and the DAP r variant were comparably virulent when animals were individually challenged. In contrast, in the coinfection model without daptomycin therapy, at both the 10 6 -and 10 7 -CFU/ml challenge inocula, the parental strain outcompeted the DAP r variant in all target organs, especially the kidneys and spleen. When the animals in the coinfection model of endocarditis were treated with DAP-gentamicin, the DAP s strain was completely eliminated, while the DAP r variant persisted in all target tissues. These data underscore that the acquisition of DAP r in S. mitis/S. oralis does come at an intrinsic fitness cost, although this resistance phenotype is completely protective against therapy with a potentially synergistic DAP regimen.

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Section: Discussionmentioning

confidence: 99%

Impact of High-Level Daptomycin Resistance in the Streptococcus mitis Group on Virulence and Survivability during Daptomycin Treatment in Experimental Infective Endocarditis

García-de-la-Mària

Xiong

Pericàs

et al. 2017

Antimicrob Agents Chemother

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“…They are either produced constitutively, for example, hBD1, or induced upon contact with pathogens, for example, hBD2 and LL-37 in keratinocytes [30]. Production of α-defensins in Paneth cells is also induced after contact with bacteria [29], and the release of platelet microbicidal proteins is induced by contact with thrombin [27].…”

Section: Human Antimicrobial Mechanismsmentioning

confidence: 99%

“…• Kinocidins are microbicidal chemokines, which are produced, for instance, by platelets [26,27]. Figure 1 shows the structures and cells or tissues of expression of some exemplary human CAMPs.…”

Section: Human Antimicrobial Mechanismsmentioning

confidence: 99%

Staphylococcus Aureus Evasion of Innate Antimicrobial Defense

Kraus

Peschel

2008

Future Microbiol.

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Bacterial pathogens colonize human body surfaces soon after birth. In order to survive the constant threat of invasion and infection, the human innate immune system has evolved several efficient mechanisms to prevent harmful microorganisms from traversing epithelial barriers. These include cationic antimicrobial peptides (CAMPs) such as defensins and the cathelicidin LL-37, bacteriolytic enzymes such as lysozyme, antimicrobial fatty acids, toxic oxygen- or nitrogen-containing molecules, the bacteriolytic complement components and further mechanisms with indirect impacts on bacterial multiplication. Staphylococcus aureus is an important human commensal and pathogen. In order to successfully establish an infection, S. aureus has evolved several mechanisms to resist the innate immune system. In this review, we focus on the mechanisms employed by S. aureus to achieve protection against antimicrobial host defense molecules with special emphasis on CAMPs. Lessons from recent studies on antimicrobial host defense molecules and cognate bacterial resistance adaptation should help in the development of more sustainable anti-infective compounds.

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“…A considerable number of excellent reviews covers several aspects of AMPs in human immunity such as the role of AMPs in the skin, [16][17][18][19][20] the AMPs present in blood cells and plasma, 21,22 platelet-derived AMPs, 23 their mode of action, 3,5,11,24 potential therapeutic applications, [25][26][27][28] integration of AMPs in the immune response 29,30 and microbial resistance against AMPs. 9,31 Here we wish to give a comprehensive overview of the currently best characterized human AMPs, putting the emphasis on their direct role in the elimination of pathogens.…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial peptides: The ancient arm of the human immune system

Wiesner¹,

Vilcinskas²

2010

Virulence

619

559

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The production of peptides and small proteins with microbicidal activity collectively called antimicrobial peptides (AMPs) is commonly considered to be a primitive mechanism of immunity and has been extensively studied in insects and other non-vertebrate organisms. In addition, a variety of AMPs present in amphibian skin secretion has been well characterised. There is now increasing evidence that AMPs play a crucial role in human immunity as well. Virtually all human tissues and cells typically exposed to microbes are able to produce AMPs. Important AMPs belonging to two structurally distinct classes, known as the defensins and the cathelicidins, are mainly produced by epithelial cells and neutrophils. AMPs significantly contributing to the chemical skin barrier are represented by dermcidin, psoriasin and RNase 7. The antimicrobial activity of saliva largely depends on histidine-rich AMPs known as histatins. Many more, in part less well-known AMPs and AMP-like proteins exist that exhibit various additional functions, apart from their antimicrobial properties. Among them, the neutrophil granule proteins azurocidin and cathepsin G are members of a family of serine-protease homologues called serprocidins and play a role in the regulation of the immune response and degradation of extracellular matrix proteins respectively. As another AMP-like protein of the neutrophil granule content, bactericidal/permeability increasing protein (BPI) is both able to permeabilise bacterial membranes and to function as an opsonin. The whey acidic protein (WAP) domain containing class of AMPs, including secretory leukocyte protease inhibitor (SLPI), elafin and trappin-2, is equally important in inhibition of neutrophil serine proteases and killing of microbes. Certain CC or CXC chemokines are known to possess antimicrobial properties and therefore are called kinocidins. Several kinocidins, including thrombocidin-1 and -2, are contained in the ?-granules of platelets. A cytoplasmic AMP described as ubiquicidin turned out to be identical with the strongly basic ribosomal protein S30. Proteolytic cleavage of the histone protein H2A in the stomach gives rise to an AMP initially described as buforin I. Adrenomedullin is a hormone-like AMP exhibiting vasodilatory and hypotensive effects. Lysozyme is mainly known for its cell wall degrading activity, but is also capable of non-enzymatic killing of bacteria. An iron-binding protein present in milk and other secretions named lactoferrin was shown to possess antimicrobial and antiviral activity and has been implicated in protection against cancer. Clinical studies on the treatment of infectious diseases have been performed with artificial peptides derived from human lactoferrin, histatins and BPI in addition to porcine protegrins, frog magains and bovine indolicidin. Omiganan, representing an indolicidin derivative, has been demonstrated to be effective in the treatment of acne and catheter-related local infections and is currently considered to be the most promising AMP-based drug candidate

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Antimicrobial Peptides Versus Invasive Infections

Cited by 26 publications

References 99 publications

Impact of High-Level Daptomycin Resistance in the Streptococcus mitis Group on Virulence and Survivability during Daptomycin Treatment in Experimental Infective Endocarditis

Impact of High-Level Daptomycin Resistance in the Streptococcus mitis Group on Virulence and Survivability during Daptomycin Treatment in Experimental Infective Endocarditis

Staphylococcus Aureus Evasion of Innate Antimicrobial Defense

Antimicrobial peptides: The ancient arm of the human immune system

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