scholarly journals A promising bioconjugate vaccine against hypervirulentKlebsiella pneumoniae

2019 ◽  
Vol 116 (37) ◽  
pp. 18655-18663 ◽  
Author(s):  
Mario F. Feldman ◽  
Anne E. Mayer Bridwell ◽  
Nichollas E. Scott ◽  
Evgeny Vinogradov ◽  
Samuel R. McKee ◽  
...  
Keyword(s):  
Capsular Polysaccharide ◽  
Multidrug Resistant ◽  
Preclinical Study ◽  
Recombinant Production ◽  
Virulent Strains ◽  
Lethal Infection ◽  
Life Threatening ◽  
Glycoconjugate Vaccines ◽  
New Generation

HypervirulentKlebsiella pneumoniae(hvKp) is globally disseminating as a community-acquired pathogen causing life-threatening infections in healthy individuals. The fact that a dose as little as 50 bacteria is lethal to mice illustrates the dramatic increase of virulence associated with hvKpstrains compared with classicalK. pneumoniae(cKp) strains, which require lethal doses greater than 107bacteria. Until recently, these virulent strains were mostly antibiotic-susceptible. However, multidrug-resistant (MDR) hvKpstrains have been emerging, spawning a new generation of hypervirulent “superbugs.” The mechanisms of hypervirulence are not fully defined, but overproduction of capsular polysaccharide significantly impedes host clearance, resulting in increased pathogenicity of hvKpstrains. While there are more than 80 serotypes ofK. pneumoniae, the K1 and K2 serotypes cause the vast majority of hypervirulent infections. Therefore, a glycoconjugate vaccine targeting these 2 serotypes could significantly reduce hvKpinfection. Conventionally, glycoconjugate vaccines are manufactured using intricate chemical methodologies to covalently attach purified polysaccharides to carrier proteins, which is widely considered to be technically challenging. Here we report on the recombinant production and analytical characterization of bioconjugate vaccines, enzymatically produced in glycoengineeredEscherichia colicells, against the 2 predominant hypervirulentK. pneumoniaeserotypes, K1 and K2. TheK. pneumoniaebioconjugates are immunogenic and efficacious, protecting mice against lethal infection from 2 hvKpstrains, NTUH K-2044 and ATCC 43816. This preclinical study constitutes a key step toward preventing further global dissemination of hypervirulent MDR hvKpstrains.

scholarly journals A novel chemical biology and computational approach to expedite the discovery of new-generation polymyxins against life-threatening Acinetobacter baumannii

2021 ◽  
Author(s):  
Xukai Jiang ◽  
Nitin A. Patil ◽  
Mohammad A. K. Azad ◽  
Hasini Wickremasinghe ◽  
Heidi Yu ◽  
...  
Keyword(s):  
Public Health ◽  
Chemical Biology ◽  
Multidrug Resistant ◽  
Computational Approach ◽  
Gram Negative Bacteria ◽  
Global Public Health ◽  
Gram Negative ◽  
Life Threatening ◽  
New Generation ◽  
Novel Antibiotics

Multidrug-resistant Gram-negative bacteria have been an urgent threat to global public health. Novel antibiotics are desperately needed to combat these 'superbugs'.

scholarly journals Isolation, Identification and Molecular Characterization of Nocardiopsaceae Producing Novel Antibiotics From Soil Samples in Bingol, Turkey

2020 ◽  
Vol 11 (2) ◽  
pp. 94
Author(s):  
Samer Abuzerr ◽  
Kate Zinszer ◽  
Syamand Ahmed Qadir ◽  
Ekrem Atalan ◽  
Halgord Ali M. Farag ◽  
...  
Keyword(s):  
Molecular Characterization ◽  
Gene Sequence ◽  
Multidrug Resistant ◽  
Physicochemical Analysis ◽  
Soil Samples ◽  
Morphological Properties ◽  
16S Rdna Gene ◽  
Life Threatening ◽  
Immense Potential

There is growing interest in the antimicrobial discovery of life-threatening multidrug-resistant pathogens. The study was undertaken to isolate, identify, and characterize antibiotic-producing actinomycetaceae, particularly nocadisosaceae, from soil samples of Bingol, Turkey. Soil samples were collected from three different regions of Bingol, Turkey. The physicochemical analysis of the soil samples was immediately measured using standard methods. This was followed by isolation of Nocardiopsaceae, nutritional tests, chemotaxonomic analysis, and molecular characterization. The isolated organisms showed morphological properties consistent with the Nocardiopsaceae soil bacteria.  The 16s rDNA gene sequence indicated a similarity between the strains with 99.86% which was Nocardiopsaceae synnemata-formans. The BLAST hits had a significant e-value of 0.005. The results of the present study revealed that soil Nocardiopsaceae of Bingol appears to have immense potential as a source of antibacterial compounds.

scholarly journals Burkholderia cepaciaComplex: Emerging Multihost Pathogens Equipped with a Wide Range of Virulence Factors and Determinants

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Sílvia A. Sousa ◽  
Christian G. Ramos ◽  
Jorge H. Leitão
Keyword(s):  
Virulence Factors ◽  
Burkholderia Cepacia ◽  
Multidrug Resistant ◽  
Human Pathogens ◽  
Closely Related Species ◽  
Oncological Patients ◽  
Wide Range ◽  
Life Threatening ◽  
Novel Therapeutic Strategies

TheBurkholderia cepaciacomplex (Bcc) comprises at least 17 closely-related species of theβ-proteobacteria subdivision, widely distributed in natural and man-made inhabitats. Bcc bacteria are endowed with an extraordinary metabolic diversity and emerged in the 1980s as life-threatening and difficult-to-treat pathogens among patients suffering from cystic fibrosis. More recently, these bacteria became recognized as a threat to hospitalized patients suffering from other diseases, in particular oncological patients. In the present paper, we review these and other traits of Bcc bacteria, as well as some of the strategies used to identify and validate the virulence factors and determinants used by these bacteria. The identification and characterization of these virulence factors is expected to lead to the design of novel therapeutic strategies to fight the infections caused by these emergent multidrug resistant human pathogens.

Physical - Chemical Issues of Cephalosporin Intercalated Nanoparticles for Life - Threatening Infections Treatment

2001 ◽  
Vol 71 (3) ◽  
pp. 342-349
Author(s):  
Lucian Eva ◽  
Letitia Doina Duceac ◽  
Liviu Stafie ◽  
Constantin Marcu ◽  
Geta Mitrea ◽  
...  
Keyword(s):  
Chemical Characterization ◽  
Advanced Characterization ◽  
Generation Cephalosporin ◽  
Fourth Generation ◽  
Exchange Method ◽  
Physico Chemical ◽  
Life Threatening ◽  
Double Hydroxide ◽  
Double Hydroxides

The fourth generation cephalosporin antibacterial agent, cefepime, was loaded into layered double hydroxides for enhancing antibiotic efficiency, reducing side effects, as well as achieving the sustained release property. The intercalation of antibiotic into the inter-gallery of ZnAl-layered double hydroxide (LDH) was carried out using ion exchange method, by this constituting a nano-sized organic-inorganic hybrid material for a controlled release novel formulation. Although cefepime is a broad spectrum antibiotic, it has various adverse effects and a significant degradation rate. Thus, the preparation and physico-chemical characterization of nanomaterials able to intercalate this drug is an important study for medical and pharmaceutical field. The antibiotic inclusion into LDHs nanostructure was confirmed by advanced characterization techniques and the release profile of cefepime was analysed with the respect to pH of the simulated media.

scholarly journals Structure, Function, and Regulation of the Essential Virulence Factor Capsular Polysaccharide of Vibrio vulnificus

2020 ◽  
Vol 21 (9) ◽  
pp. 3259 ◽  
Author(s):  
Gregg S. Pettis ◽  
Aheli S. Mukerji
Keyword(s):  
Coastal Waters ◽  
Capsular Polysaccharide ◽  
Vibrio Vulnificus ◽  
Critical Role ◽  
Phase Variation ◽  
Innate Immune ◽  
Repeat Sequences ◽  
Life Threatening ◽  
Inflammatory Cytokine Response ◽  
Group 1

Vibrio vulnificus populates coastal waters around the world, where it exists freely or becomes concentrated in filter feeding mollusks. It also causes rapid and life-threatening sepsis and wound infections in humans. Of its many virulence factors, it is the V. vulnificus capsule, composed of capsular polysaccharide (CPS), that plays a critical role in evasion of the host innate immune system by conferring antiphagocytic ability and resistance to complement-mediated killing. CPS may also provoke a portion of the host inflammatory cytokine response to this bacterium. CPS production is biochemically and genetically diverse among strains of V. vulnificus, and the carbohydrate diversity of CPS is likely affected by horizontal gene transfer events that result in new combinations of biosynthetic genes. Phase variation between virulent encapsulated opaque colonial variants and attenuated translucent colonial variants, which have little or no CPS, is a common phenotype among strains of this species. One mechanism for generating acapsular variants likely involves homologous recombination between repeat sequences flanking the wzb phosphatase gene within the Group 1 CPS biosynthetic and transport operon. A considerable number of environmental, genetic, and regulatory factors have now been identified that affect CPS gene expression and CPS production in this pathogen.

scholarly journals Recombinant Production and Characterization of an Extracellular Subtilisin-Like Serine Protease from Acinetobacter baumannii of Fermented Food Origin

2021 ◽  
Author(s):  
Nur Syafiqah Muhammed ◽  
Nurulfarhana Hussin ◽  
Aik Siang Lim ◽  
Mohd Anuar Jonet ◽  
Shaza Eva Mohamad ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Serine Protease ◽  
Fermented Food ◽  
Recombinant Production

scholarly journals Radiation-Inactivated Acinetobacter baumannii Vaccine Candidates

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 96
Author(s):  
Stephen J. Dollery ◽  
Daniel V. Zurawski ◽  
Elena K. Gaidamakova ◽  
Vera Y. Matrosova ◽  
John K. Tobin ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Treatment Options ◽  
Bacterial Pathogen ◽  
Multidrug Resistant ◽  
Bacterial Cells ◽  
Wound Infections ◽  
Protein Profiles ◽  
Vaccine Candidates ◽  
Rich Media ◽  
Life Threatening

Acinetobacter baumannii is a bacterial pathogen that is often multidrug-resistant (MDR) and causes a range of life-threatening illnesses, including pneumonia, septicemia, and wound infections. Some antibiotic treatments can reduce mortality if dosed early enough before an infection progresses, but there are few other treatment options when it comes to MDR-infection. Although several prophylactic strategies have been assessed, no vaccine candidates have advanced to clinical trials or have been approved. Herein, we rapidly produced protective whole-cell immunogens from planktonic and biofilm-like cultures of A. baumannii, strain AB5075 grown using a variety of methods. After selecting a panel of five cultures based on distinct protein profiles, replicative activity was extinguished by exposure to 10 kGy gamma radiation in the presence of a Deinococcus antioxidant complex composed of manganous (Mn2+) ions, a decapeptide, and orthophosphate. Mn2+ antioxidants prevent hydroxylation and carbonylation of irradiated proteins, but do not protect nucleic acids, yielding replication-deficient immunogenic A. baumannii vaccine candidates. Mice were immunized and boosted twice with 1.0 × 107 irradiated bacterial cells and then challenged intranasally with AB5075 using two mouse models. Planktonic cultures grown for 16 h in rich media and biofilm cultures grown in static cultures underneath minimal (M9) media stimulated immunity that led to 80–100% protection.

scholarly journals S. pseudintermedius and S. aureus lineages with transmission ability circulate as causative agents of infections in pets for years

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Laura Ruiz-Ripa ◽  
Carmen Simón ◽  
Sara Ceballos ◽  
Carmelo Ortega ◽  
Myriam Zarazaga ◽  
...  
Keyword(s):  
Treatment Options ◽  
Companion Animals ◽  
Clinical History ◽  
Multidrug Resistant ◽  
Hospital Environment ◽  
Antimicrobial Resistance Profile ◽  
Causative Agents ◽  
Veterinary Hospital ◽  
Coagulase Positive Staphylococci

Abstract Background Staphylococcus pseudintermedius (SP) and Staphylococcus aureus (SA) are common colonizers of companion animals, but they are also considered opportunistic pathogens, causing diseases of diverse severity. This study focused on the identification and characterization of 33 coagulase-positive staphylococci isolated from diseased pets (28 dogs and five cats) during 2009–2011 in a veterinary hospital in Spain in order to stablish the circulating lineages and their antimicrobial resistance profile. Results Twenty-eight isolates were identified as SP and five as SA. Nine methicillin-resistant (MR) isolates (27%) carrying the mecA gene were detected (eight MRSP and one MRSA). The 55% of SP and SA isolates were multidrug-resistant (MDR). MRSP strains were typed as ST71-agrIII-SCCmecII/III-(PFGE) A (n=5), ST68-agrIV-SCCmecV-B1/B2 (n=2), and ST258-agrII-SCCmecIV-C (n=1). SP isolates showed resistance to the following antimicrobials [percentage of resistant isolates/resistance genes]: penicillin [82/blaZ], oxacillin [29/mecA] erythromycin/clindamycin [43/erm(B)], aminoglycosides [18–46/aacA-aphD, aphA3, aadE], tetracycline [71/tet(M), tet(K)], ciprofloxacin [29], chloramphenicol [29/catpC221], and trimethoprim-sulfamethoxazole [50/dfrG, dfrK]. The dfrK gene was revealed as part of the radC-integrated Tn559 in two SP isolates. Virulence genes detected among SP isolates were as follow [percentage of isolates]: siet [100], se-int [100], lukS/F-I [100], seccanine [7], and expB [7]. The single MRSA-mecA detected was typed as t011-ST398/CC398-agrI-SCCmecV and was MDR. The methicillin-susceptible SA isolates were typed as t045-ST5/CC5 (n=2), t10576-ST1660 (n=1), and t005-ST22/CC22 (n=1); the t005-ST22 feline isolate was PVL-positive and the two t045-ST45 isolates were ascribed to Immune Evasion Cluster (IEC) type F. Moreover, the t10576-ST1660 isolate, of potential equine origin, harbored the lukPQ and scneq genes. According to animal clinical history and data records, several strains seem to have been acquired from different sources of the hospital environment, while some SA strains appeared to have a human origin. Conclusions The frequent detection of MR and MDR isolates among clinical SP and SA strains with noticeable virulence traits is of veterinary concern, implying limited treatment options available. This is the first description of MRSA-ST398 and MRSP-ST68 in pets in Spain, as well the first report of the dfrK-carrying Tn559 in SP. This evidences that current transmissible lineages with mobilizable resistomes have been circulating as causative agents of infections among pets for years.

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