scholarly journals Increase in Antibiotic-Resistant Gram-Negative Bacterial Infections in Febrile Neutropenic Children

2016 ◽  
Vol 48 (3) ◽  
pp. 181 ◽  
Author(s):  
Joon Hee Lee ◽  
Seul-Ki Kim ◽  
Seong Koo Kim ◽  
Seung Beom Han ◽  
Jae Wook Lee ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Antibiotic Resistant ◽  
Gram Negative

scholarly journals TSPphg Lysin from the Extremophilic Thermus Bacteriophage TSP4 as a Potential Antimicrobial Agent against Both Gram-Negative and Gram-Positive Pathogenic Bacteria

Viruses ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 192 ◽  
Author(s):  
Feng Wang ◽  
Xinyu Ji ◽  
Qiupeng Li ◽  
Guanling Zhang ◽  
Jiani Peng ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Infection Model ◽  
Bacterial Cells ◽  
Skin Damage ◽  
Gram Positive ◽  
Antibiotic Resistant ◽  
Gram Negative

New strategies against antibiotic-resistant bacterial pathogens are urgently needed but are not within reach. Here, we present in vitro and in vivo antimicrobial activity of TSPphg, a novel phage lysin identified from extremophilic Thermus phage TSP4 by sequencing its whole genome. By breaking down the bacterial cells, TSPphg is able to cause bacteria destruction and has shown bactericidal activity against both Gram-negative and Gram-positive pathogenic bacteria, especially antibiotic-resistant strains of Klebsiella pneumoniae, in which the complete elimination and highest reduction in bacterial counts by greater than 6 logs were observed upon 50 μg/mL TSPphg treatment at 37 °C for 1 h. A murine skin infection model further confirmed the in vivo efficacy of TSPphg in removing a highly dangerous and multidrug-resistant Staphylococcus aureus from skin damage and in accelerating wound closure. Together, our findings may offer a therapeutic alternative to help fight bacterial infections in the current age of mounting antibiotic resistance, and to shed light on bacteriophage-based strategies to develop novel anti-infectives.

scholarly journals Pilicide ec240 Disrupts Virulence Circuits in Uropathogenic Escherichia coli

mBio ◽  
2014 ◽  
Vol 5 (6) ◽  
Author(s):  
Sarah E. Greene ◽  
Jerome S. Pinkner ◽  
Erik Chorell ◽  
Karen W. Dodson ◽  
Carrie L. Shaffer ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Virulence Factors ◽  
Bacterial Infections ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
Content Type ◽  
Pilus Biogenesis ◽  
Altered Regulation ◽  
Tract Infections

ABSTRACTChaperone-usher pathway (CUP) pili are extracellular organelles produced by Gram-negative bacteria that mediate bacterial pathogenesis. Small-molecule inhibitors of CUP pili, termed pilicides, were rationally designed and shown to inhibit type 1 or P piliation. Here, we show that pilicide ec240 decreased the levels of type 1, P, and S piliation. Transcriptomic and proteomic analyses using the cystitis isolate UTI89 revealed that ec240 dysregulated CUP pili and decreased motility. Paradoxically, the transcript levels of P and S pilus genes were increased during growth in ec240, even though the level of P and S piliation decreased. In contrast, the most downregulated transcripts after growth in ec240 were from the type 1 pilus genes. Type 1 pilus expression is controlled by inversion of thefimSpromoter element, which can oscillate between phase on and phase off orientations. ec240 induced thefimSphase off orientation, and this effect was necessary for the majority of ec240’s inhibition of type 1 piliation. ec240 increased levels of the transcriptional regulators SfaB and PapB, which were shown to induce thefimSpromoter phase off orientation. Furthermore, the effect of ec240 on motility was abolished in the absence of the SfaB, PapB, SfaX, and PapX regulators. In contrast to the effects of ec240, deletion of the type 1 pilus operon led to increased S and P piliation and motility. Thus, ec240 dysregulated several uropathogenicEscherichia coli(UPEC) virulence factors through different mechanisms and independent of its effects on type 1 pilus biogenesis and may have potential as an antivirulence compound.IMPORTANCECUP pili and flagella play active roles in the pathogenesis of a variety of Gram-negative bacterial infections, including urinary tract infections mediated by UPEC. These are extremely common infections that are often recurrent and increasingly caused by antibiotic-resistant organisms. Preventing piliation and motility through altered regulation and assembly of these important virulence factors could aid in the development of novel therapeutics. This study increases our understanding of the regulation of these virulence factors, providing new avenues by which to target their expression.

scholarly journals Antimicrobial Peptide Novicidin Synergizes with Rifampin, Ceftriaxone, and Ceftazidime against Antibiotic-Resistant EnterobacteriaceaeIn Vitro

2015 ◽  
Vol 59 (10) ◽  
pp. 6233-6240 ◽  
Author(s):  
Odel Soren ◽  
Karoline Sidelmann Brinch ◽  
Dipesh Patel ◽  
Yingjun Liu ◽  
Alexander Liu ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
Bacterial Infections ◽  
New Drugs ◽  
Gram Negative Bacteria ◽  
Cationic Antimicrobial Peptide ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
Resistant Strains ◽  
Multiple Strains

ABSTRACTThe spread of antibiotic resistance among Gram-negative bacteria is a serious clinical threat, and infections with these organisms are a leading cause of mortality worldwide. Traditional novel drug development inevitably leads to the emergence of new resistant strains, rendering the new drugs ineffective. Therefore, reviving the therapeutic potentials of existing antibiotics represents an attractive novel strategy. Novicidin, a novel cationic antimicrobial peptide, is effective against Gram-negative bacteria. Here, we investigated novicidin as a possible antibiotic enhancer. The actions of novicidin in combination with rifampin, ceftriaxone, or ceftazidime were investigated against 94 antibiotic-resistant clinical Gram-negative isolates and 7 strains expressing New Delhi metallo-β-lactamase-1. Using the checkerboard method, novicidin combined with rifampin showed synergy with >70% of the strains, reducing the MICs significantly. The combination of novicidin with ceftriaxone or ceftazidime was synergistic against 89.7% of the ceftriaxone-resistant strains and 94.1% of the ceftazidime-resistant strains. Synergistic interactions were confirmed using time-kill studies with multiple strains. Furthermore, novicidin increased the postantibiotic effect when combined with rifampin or ceftriaxone. Membrane depolarization assays revealed that novicidin alters the cytoplasmic membrane potential of Gram-negative bacteria.In vitrotoxicology tests showed novicidin to have low hemolytic activity and no detrimental effect on cell cultures. We demonstrated that novicidin strongly rejuvenates the therapeutic potencies of ceftriaxone or ceftazidime against resistant Gram-negative bacteriain vitro. In addition, novicidin boosted the activity of rifampin. This strategy can have major clinical implications in our fight against antibiotic-resistant bacterial infections.

scholarly journals The therapeutic potential of bacteriocins as protein antibiotics

2017 ◽  
Vol 1 (1) ◽  
pp. 65-74 ◽  
Author(s):  
Hannah M. Behrens ◽  
Anne Six ◽  
Daniel Walker ◽  
Colin Kleanthous
Keyword(s):  
Bacterial Infections ◽  
Therapeutic Potential ◽  
Ecological Niches ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
Novel Treatments ◽  
Study Results ◽  
Protein Toxins

The growing incidence of antibiotic-resistant Gram-negative bacterial infections poses a serious threat to public health. Molecules that have yet to be exploited as antibiotics are potent protein toxins called bacteriocins that are produced by Gram-negative bacteria during competition for ecological niches. This review discusses the state of the art regarding the use for therapeutic purposes of two types of Gram-negative bacteriocins: colicin-like bacteriocins (CLBs) and tailocins. In addition to in vitro data, the potency of eight identified CLBs or tailocins has been demonstrated in diverse animal models of infection with no adverse effects for the host. Although the characteristics of bacteriocins will need further study, results obtained thus far regarding their in vivo potency, immunogenicity and low levels of resistance are encouraging. This leads the way for the development of novel treatments using bacteriocins as protein antibiotics.

scholarly journals Antibiotic-Resistant Gram-Negative Bacterial Infections in Patients With Cancer

2014 ◽  
Vol 59 (suppl_5) ◽  
pp. S335-S339 ◽  
Author(s):  
Federico Perez ◽  
Javier Adachi ◽  
Robert A. Bonomo
Keyword(s):  
Bacterial Infections ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
Patients With Cancer
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