DALAFLOXACIN- ANTIBACTERIAL: A REVIEW

Antibiotics (from ancient Greek αντιβιοτικά, antiviotika), also called antibacterials, are a type of antimicrobials drug used in the treatment and prevention of bacterial infections. Cellulitis is an infection that involves the outer layers of the skin. It is commonly caused by bacteria known as beta-hemolytic streptococcus or Staphylococcus aureus. You may experience pain, swelling, tenderness, warmth, and redness in the infected area. Complicate skin and soft tissue infections (SSTIs) are common for both outpatient and hospitalized patients and traditionally include various clinical symptoms ranging from minor superficial infections to necrotizing fasciitis with high rates of mortality. Delafloxacin (DLX) is a new FQ pending approval, which has shown a good in vitro and in vivo activity against major pathogens associated with ABSSSIs and CA-RTIs. It also shows good activity against a broad spectrum of microorganisms, including those resistant to other FQ, and stability against multiresistant strains.

Download Full-text

Mammary gland 3D cell culture systems in farm animals

Veterinary Research ◽

10.1186/s13567-021-00947-5 ◽

2021 ◽

Vol 52 (1) ◽

Author(s):

Laurence Finot ◽

Eric Chanat ◽

Frederic Dessauge

Keyword(s):

Cell Culture ◽

Mammary Gland ◽

Bacterial Infections ◽

Three Dimensional ◽

3D Cell Culture ◽

Farm Animals ◽

Culture Systems ◽

Cell Culture Systems

AbstractIn vivo study of tissue or organ biology in mammals is very complex and progress is slowed by poor accessibility of samples and ethical concerns. Fortunately, however, advances in stem cell identification and culture have made it possible to derive in vitro 3D “tissues” called organoids, these three-dimensional structures partly or fully mimicking the in vivo functioning of organs. The mammary gland produces milk, the source of nutrition for newborn mammals. Milk is synthesized and secreted by the differentiated polarized mammary epithelial cells of the gland. Reconstructing in vitro a mammary-like structure mimicking the functional tissue represents a major challenge in mammary gland biology, especially for farm animals for which specific agronomic questions arise. This would greatly facilitate the study of mammary gland development, milk secretion processes and pathological effects of viral or bacterial infections at the cellular level, all with the objective of improving milk production at the animal level. With this aim, various 3D cell culture models have been developed such as mammospheres and, more recently, efforts to develop organoids in vitro have been considerable. Researchers are now starting to draw inspiration from other fields, such as bioengineering, to generate organoids that would be more physiologically relevant. In this chapter, we will discuss 3D cell culture systems as organoids and their relevance for agronomic research.

Download Full-text

Is There Potential for Repurposing Statins as Novel Antimicrobials?

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00192-16 ◽

2016 ◽

Vol 60 (9) ◽

pp. 5111-5121 ◽

Cited By ~ 52

Author(s):

Emma Hennessy ◽

Claire Adams ◽

F. Jerry Reen ◽

Fergal O'Gara

Keyword(s):

Serum Cholesterol ◽

Bacterial Growth ◽

Bacterial Infections ◽

Statin Treatment ◽

Therapeutic Agents ◽

Pleiotropic Effects ◽

Current Information ◽

Potential Use

ABSTRACTStatins are members of a class of pharmaceutical widely used to reduce high levels of serum cholesterol. In addition, statins have so-called “pleiotropic effects,” which include inflammation reduction, immunomodulation, and antimicrobial effects. An increasing number of studies are emerging which detail the attenuation of bacterial growth andin vitroandin vivovirulence by statin treatment. In this review, we describe the current information available concerning the effects of statins on bacterial infections and provide insight regarding the potential use of these compounds as antimicrobial therapeutic agents.

Download Full-text

Bacteriocins of Non-aureus Staphylococci Isolated from Bovine Milk

Applied and Environmental Microbiology ◽

10.1128/aem.01015-17 ◽

2017 ◽

Vol 83 (17) ◽

Cited By ~ 24

Author(s):

Domonique A. Carson ◽

Herman W. Barkema ◽

Sohail Naushad ◽

Jeroen De Buck

Keyword(s):

Staphylococcus Aureus ◽

Bacterial Infections ◽

Genome Mining ◽

Bovine Milk ◽

Gene Clusters ◽

Antibiotic Use ◽

Content Type ◽

Treatment And Prevention ◽

Whole Genomes

ABSTRACT Non-aureus staphylococci (NAS), the bacteria most commonly isolated from the bovine udder, potentially protect the udder against infection by major mastitis pathogens due to bacteriocin production. In this study, we determined the inhibitory capability of 441 bovine NAS isolates (comprising 26 species) against bovine Staphylococcus aureus. Furthermore, inhibiting isolates were tested against a human methicillin-resistant S. aureus (MRSA) isolate using a cross-streaking method. We determined the presence of bacteriocin clusters in NAS whole genomes using genome mining tools, BLAST, and comparison of genomes of closely related inhibiting and noninhibiting isolates and determined the genetic organization of any identified bacteriocin biosynthetic gene clusters. Forty isolates from 9 species (S. capitis, S. chromogenes, S. epidermidis, S. pasteuri, S. saprophyticus, S. sciuri, S. simulans, S. warneri, and S. xylosus) inhibited growth of S. aureus in vitro, 23 isolates of which, from S. capitis, S. chromogenes, S. epidermidis, S. pasteuri, S. simulans, and S. xylosus, also inhibited MRSA. One hundred five putative bacteriocin gene clusters encompassing 6 different classes (lanthipeptides, sactipeptides, lasso peptides, class IIa, class IIc, and class IId) in 95 whole genomes from 16 species were identified. A total of 25 novel bacteriocin precursors were described. In conclusion, NAS from bovine mammary glands are a source of potential bacteriocins, with >21% being possible producers, representing potential for future characterization and prospective clinical applications. IMPORTANCE Mastitis (particularly infections caused by Staphylococcus aureus) costs Canadian dairy producers $400 million/year and is the leading cause of antibiotic use on dairy farms. With increasing antibiotic resistance and regulations regarding use, there is impetus to explore bacteriocins (bacterially produced antimicrobial peptides) for treatment and prevention of bacterial infections. We examined the ability of 441 NAS bacteria from Canadian bovine milk samples to inhibit growth of S. aureus in the laboratory. Overall, 9% inhibited growth of S. aureus and 58% of those also inhibited MRSA. In NAS whole-genome sequences, we identified >21% of NAS as having bacteriocin genes. Our study represents a foundation to further explore NAS bacteriocins for clinical use.

Download Full-text

Evaluation of the Efficacy of a Bacteriophage in the Treatment of Pneumonia Induced by Multidrug ResistanceKlebsiella pneumoniaein Mice

BioMed Research International ◽

10.1155/2015/752930 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 41

Author(s):

Fang Cao ◽

Xitao Wang ◽

Linhui Wang ◽

Zhen Li ◽

Jian Che ◽

...

Keyword(s):

Bacterial Infections ◽

Burst Size ◽

Multidrug Resistant ◽

Lung Lesion ◽

Lytic Bacteriophage ◽

Short Latent Period ◽

Dose Dependent ◽

Antibiotic Control

Multidrug-resistantKlebsiella pneumoniae(MRKP) has steadily grown beyond antibiotic control. However, a bacteriophage is considered to be a potential antibiotic alternative for treating bacterial infections. In this study, a lytic bacteriophage, phage 1513, was isolated using a clinical MRKP isolate KP 1513 as the host and was characterized. It produced a clear plaque with a halo and was classified as Siphoviridae. It had a short latent period of 30 min, a burst size of 264 and could inhibit KP 1513 growthin vitrowith a dose-dependent pattern. Intranasal administration of a single dose of 2 × 109 PFU/mouse 2 h after KP 1513 inoculation was able to protect mice against lethal pneumonia. In a sublethal pneumonia model, phage-treated mice exhibited a lower level ofK. pneumoniaeburden in the lungs as compared to the untreated control. These mice lost less body weight and exhibited lower levels of inflammatory cytokines in their lungs. Lung lesion conditions were obviously improved by phage therapy. Therefore, phage 1513 has a great effectin vitroandin vivo, which has potential to be used as an alternative to an antibiotic treatment of pneumonia that is caused by the multidrug-resistantK. pneumoniae.

Download Full-text

Local Immune Responses to Chlamydia pneumoniae in the Lungs of BALB/c Mice during Primary Infection and Reinfection

Infection and Immunity ◽

10.1128/iai.66.11.5113-5118.1998 ◽

1998 ◽

Vol 66 (11) ◽

pp. 5113-5118 ◽

Cited By ~ 46

Author(s):

Jenni M. Penttilä ◽

Marjukka Anttila ◽

Mirja Puolakkainen ◽

Aino Laurila ◽

Kari Varkila ◽

...

Keyword(s):

Primary Infection ◽

Bacterial Infections ◽

Chlamydia Pneumoniae ◽

Mononuclear Cells ◽

Relative Increase ◽

Culturable Bacteria ◽

Ifn Γ ◽

Tissue Reactions

ABSTRACT Cell-mediated immune (CMI) responses play a major role in protection as well as pathogenesis of many intracellular bacterial infections. In this study, we evaluated the infection kinetics and assessed histologically the lymphoid reactions and local, in vitro-restimulated CMI responses in lungs of BALB/c mice, during both primary infection and reinfection with Chlamydia pneumoniae. The primary challenge resulted in a self-restricted infection with elimination of culturable bacteria by day 27 after challenge. A mild lymphoid reaction characterized the pathology in the lungs. In vitro CMI responses consisted of a weak proliferative response and no secretion of gamma interferon (IFN-γ). The number of lung-derived mononuclear cells increased substantially during the primary infection; the largest relative increase was observed in B cells (B220+). After reinfection, the number of lung-derived mononuclear cells increased further, and the response consisted mainly of T cells. The reinfection was characterized in vivo by significant protection from infection (fewer cultivable bacteria in the lungs for a shorter period of time) but increased local lymphoid reaction at the infection site. In vitro, as opposed to the response in naive mice, acquired immunity was characterized by a strongly Th1-biased (IFN-γ) CMI response. These results suggest that repeated infections with C. pneumoniae may induce Th1-type responses with similar associated tissue reactions, as shown in C. trachomatis infection models.

Download Full-text

Advances in lactoferrin research concerning bovine mastitis

Biochemistry and Cell Biology ◽

10.1139/bcb-2016-0044 ◽

2017 ◽

Vol 95 (1) ◽

pp. 69-75 ◽

Cited By ~ 7

Author(s):

Kei-ichi Shimazaki ◽

Kazuhiro Kawai

Keyword(s):

Immune System ◽

Defense Mechanism ◽

Bovine Mastitis ◽

Healthy Development ◽

Treatment And Prevention ◽

Year 2000 ◽

Mastitis Pathogens ◽

Binding Glycoprotein

Lactoferrin is a multifunctional, iron-binding glycoprotein found in milk and other exocrine secretions. Lactoferrin in milk plays vital roles in the healthy development of newborn mammals, and is also an innate resistance factor involved in the prevention of mammary gland infection by microorganisms. Inflammation of the udder because of bacterial infection is referred to as mastitis. There have been many investigations into the relationships between lactoferrin and mastitis, which fall into several categories. The main categories are fluctuations in the lactoferrin concentration of milk, lactoferrin activity against mastitis pathogens, elucidation of the processes underlying the onset of mastitis, participation of lactoferrin in the immune system, and utilization of lactoferrin in mastitis treatment and prevention. This minireview describes lactoferrin research concerning bovine mastitis. In the 1970s, many researchers reported that the lactoferrin concentration fluctuates in milk from cows with mastitis. From the late 1980s, many studies clarified the infection-defense mechanism in the udder and the contribution of lactoferrin to the immune system. After the year 2000, the processes underlying the onset of mastitis were elucidated in vivo and in vitro, and lactoferrin was applied for the treatment and prevention of mastitis.

Download Full-text

Preclinical Research in McArdle Disease: A Review of Research Models and Therapeutic Strategies

Genes ◽

10.3390/genes13010074 ◽

2021 ◽

Vol 13 (1) ◽

pp. 74

Author(s):

Mónica Villarreal-Salazar ◽

Astrid Brull ◽

Gisela Nogales-Gadea ◽

Antoni L. Andreu ◽

Miguel A. Martín ◽

...

Keyword(s):

Clinical Symptoms ◽

Autosomal Recessive Disorder ◽

Glycogen Metabolism ◽

Preclinical Models ◽

Preclinical Research ◽

Mcardle Disease ◽

Invasive Techniques ◽

Insight Into

McArdle disease is an autosomal recessive disorder of muscle glycogen metabolism caused by pathogenic mutations in the PYGM gene, which encodes the skeletal muscle-specific isoform of glycogen phosphorylase. Clinical symptoms are mainly characterized by transient acute “crises” of early fatigue, myalgia and contractures, which can be accompanied by rhabdomyolysis. Owing to the difficulty of performing mechanistic studies in patients that often rely on invasive techniques, preclinical models have been used for decades, thereby contributing to gain insight into the pathophysiology and pathobiology of human diseases. In the present work, we describe the existing in vitro and in vivo preclinical models for McArdle disease and review the insights these models have provided. In addition, despite presenting some differences with the typical patient’s phenotype, these models allow for a deep study of the different features of the disease while representing a necessary preclinical step to assess the efficacy and safety of possible treatments before they are tested in patients.

Download Full-text

Antidiabetic Effects of Hydroxytyrosol: In Vitro and In Vivo Evidence

Antioxidants ◽

10.3390/antiox8060188 ◽

2019 ◽

Vol 8 (6) ◽

pp. 188 ◽

Cited By ~ 10

Author(s):

Filip Vlavcheski ◽

Mariah Young ◽

Evangelia Tsiani

Keyword(s):

Insulin Resistance ◽

Pathological Condition ◽

Current Treatment ◽

In Vivo Studies ◽

Olive Leaves ◽

Treatment And Prevention ◽

Antidiabetic Effects

Insulin resistance, a pathological condition characterized by defects in insulin action leads to the development of Type 2 diabetes mellitus (T2DM), a disease which is currently on the rise that pose an enormous economic burden to healthcare systems worldwide. The current treatment and prevention strategies are considerably lacking in number and efficacy and therefore new targeted therapies and preventative strategies are urgently needed. Plant-derived chemicals such as metformin, derived from the French lilac, have been used to treat/manage insulin resistance and T2DM. Other plant-derived chemicals which are not yet discovered, may have superior properties to prevent and manage T2DM and thus research into this area is highly justifiable. Hydroxytyrosol is a phenolic phytochemical found in olive leaves and olive oil reported to have antioxidant, anti-inflammatory, anticancer and antidiabetic properties. The present review summarizes the current in vitro and in vivo studies examining the antidiabetic properties of hydroxytyrosol and investigating the mechanisms of its action.

Download Full-text

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

Viruses ◽

10.3390/v12020192 ◽

2020 ◽

Vol 12 (2) ◽

pp. 192 ◽

Cited By ~ 6

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.

Download Full-text

Efficacy of Bacteriophages Against Staphylococcus aureus Isolates from Bovine Mastitis

Pharmaceuticals ◽

10.3390/ph13030035 ◽

2020 ◽

Vol 13 (3) ◽

pp. 35 ◽

Cited By ~ 2

Author(s):

Isabel Titze ◽

Tatiana Lehnherr ◽

Hansjörg Lehnherr ◽

Volker Krömker

Keyword(s):

Staphylococcus Aureus ◽

Host Range ◽

Bacterial Infections ◽

Plaque Assay ◽

Bovine Milk ◽

Bovine Mastitis ◽

Raw Milk ◽

Pasteurized Milk

The lytic efficacy of bacteriophages against Staphylococcus aureus isolates from bovine milk was investigated in vitro, regarding possible applications in the therapy of udder inflammation caused by bacterial infections (mastitis). The host range of sequenced, lytic bacteriophages was determined against a collection of 92 Staphylococcus (S.) aureus isolates. The isolates originated from quarter foremilk samples of clinical and subclinical mastitis cases. A spot test and a subsequent plaque assay were used to determine the phage host range. According to their host range, propagation and storage properties, three phages, STA1.ST29, EB1.ST11, and EB1.ST27, were selected for preparing a bacteriophage mixture (1:1:1), which was examined for its lytic activity against S. aureus in pasteurized and raw milk. It was found that almost two thirds of the isolates could be lysed by at least one of the tested phages. The bacteriophage mixture was able to reduce the S. aureus germ density in pasteurized milk and its reduction ability was maintained in raw milk, with only a moderate decrease compared to the results in pasteurized milk. The significant reduction ability of the phage mixture in raw milk promotes further in vivo investigation.

Download Full-text