Novel Strategies for the Treatment of<i>Pseudomonas aeruginosa</i>Infections

Wagner, Stefanie; Sommer, Roman; Hinsberger, Stefan; Lu, Cenbin; Hartmann, Rolf W.; Empting, Martin; Titz, Alexander

doi:10.1021/acs.jmedchem.5b01698

Cited by 219 publications

(254 citation statements)

References 406 publications

(788 reference statements)

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“…As discussed in previous reports [26–29], a promising new class of antipathogenic drugs that target virulence factors and/or biofilm formation instead of killing the pathogens has many advantages in clinical use. First, these antipathogenic drugs theoretically are less likely to render drug resistance in the pathogens because they do not assert a selective pressure on the pathogen's survival.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of Pseudomonas aeruginosa Biofilm Formation by Traditional Chinese Medicinal Herb Herba patriniae

Dang

et al. 2017

BioMed Research International

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New antimicrobial agents are urgently needed to treat infections caused by drug-resistant pathogens and by pathogens capable of persisting in biofilms. The aim of this study was to identify traditional Chinese herbs that could inhibit biofilm formation of Pseudomonas aeruginosa, an important human pathogen that causes serious and difficult-to-treat infections in humans. A luxCDABE-based reporter system was constructed to monitor the expression of six key biofilm-associated genes in P. aeruginosa. The reporters were used to screen a library of 36 herb extracts for inhibitory properties against these genes. The results obtained indicated that the extract of Herba patriniae displayed significant inhibitory effect on almost all of these biofilm-associated genes. Quantitative analysis showed that H. patriniae extract was able to significantly reduce the biofilm formation and dramatically altered the structure of the mature biofilms of P. aeruginosa. Further studies showed H. patriniae extract decreased exopolysaccharide production by P. aeruginosa and promoted its swarming motility, two features disparately associated with biofilm formation. These results provided a potential mechanism for the use of H. patriniae to treat bacterial infections by traditional Chinese medicines and revealed a promising candidate for exploration of new drugs against P. aeruginosa biofilm-associated infections.

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Section: Resultsmentioning

confidence: 99%

Inhibition of Pseudomonas aeruginosa Biofilm Formation by Traditional Chinese Medicinal Herb Herba patriniae

Dang

et al. 2017

BioMed Research International

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“…Among the bacterial species with low abundance, we also found that K . marxianus addition at high dose decreased the abundance of Rickettsiales , Pseudomonadales and Acinetobacter junii , which are defined as pernicious gut microorganisms that induce a variety of disorders of host [54–57]. Thus, it could be assumed that there was a connection between the reduced harmful germs in gut and the improved intestinal health of birds after K .…”

Section: Discussionmentioning

confidence: 99%

Effects of Kluyveromyces marxianus supplementation on immune responses, intestinal structure and microbiota in broiler chickens

Wang

et al. 2017

PLoS ONE

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To investigate the effects of Kluyveromyces marxianus on immune responses, intestinal structure and microbiota in broilers, 840 1-d-old broiler chicks were randomly divided into seven groups (eight replicates) and were fed basal diets without or with 0.25, 0.50, 1.0, 1.5, 2.0, and 2.5 g/kg of K. marxianus (2.0×1010 CFU/g). Serum and intestine samples were collected at 21 d of age. The results showed that increasing K. marxianus addition linearly reduced feed conversion ratio but linearly elevated relative thymus weight, as well as quadratically increased serum lysozyme and IgG levels, with the medium dose (1.0 g/kg) being the most effective. The ratio of villus height to crypt depth of jejunum and ileum, ileal villus height and sucrase activity, as well as the mRNA expression of ileal mucin-2, claudin-1 and sodium glucose cotransporter 1 linearly responded to the increasing K. marxianus addition. Supplemental K. marxianus at low (0.5 g/kg), medium (1.5 g/kg) and high (2.5 g/kg) dose all decreased the abundance of phylum Cyanobacteria, increased the abundance of phylum Firmicutes and genus Lactobacillus in ileum. The high dose of K. marxianus addition also reduced the abundance of order Rickettsiales and Pseudomonadales along with species Acinetobacter junii. Ileal bacterial communities between K. marxianus-treated and untreated groups formed distinctly different clusters. In summary, K. marxianus supplementation benefits feed efficiency and immune function, as well as intestinal structure in broilers, which might be attributed to the improved ileal microbial structure. Supplemental K. marxianus at high dose (2.5 g/kg) was more effective for feed efficiency and intestinal health of broilers, while the innate immunity was optimized at a medium dose (1.0 g/kg).

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“…Anti-biofilm inhibitors targeting carbohydrate-binding lectins show good potency in vitro and in vivo , but might disrupt host lectins [27,36]. Type IV pili [37] are unsuitable targets because they are not well-conserved in P. aeruginosa isolates.…”

Section: Anti-virulence Strategies For P Aeruginosamentioning

confidence: 99%

Considerations and caveats in anti-virulence drug development

Maura

Ballok

Rahme

2016

Current Opinion in Microbiology

123

110

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As antibiotic resistance remains a major public health threat, anti-virulence therapy research is gaining interest. Hundreds of potential anti-virulence compounds have been examined, but very few have made it to clinical trials and none have been approved. This review surveys the current anti-virulence research field with a focus on the highly resistant and deadly ESKAPE pathogens, especially Pseudomonas aeruginosa. We discuss timely considerations and caveats in anti-virulence drug development, including target identification, administration, preclinical development, and metrics for success in clinical trials. Development of a defined pipeline for anti-virulence agents, which differs in important ways from conventional antibiotics, is imperative for the future success of these critically needed drugs.

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Novel Strategies for the Treatment ofPseudomonas aeruginosaInfections

Cited by 219 publications

References 406 publications

Inhibition of Pseudomonas aeruginosa Biofilm Formation by Traditional Chinese Medicinal Herb Herba patriniae

Inhibition of Pseudomonas aeruginosa Biofilm Formation by Traditional Chinese Medicinal Herb Herba patriniae

Effects of Kluyveromyces marxianus supplementation on immune responses, intestinal structure and microbiota in broiler chickens

Considerations and caveats in anti-virulence drug development

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