scholarly journals Hydrophilic nanoparticles that kill bacteria while sparing mammalian cells reveal the antibiotic role of nanostructures

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Yunjiang Jiang ◽  
Wan Zheng ◽  
Keith Tran ◽  
Elizabeth Kamilar ◽  
Jitender Bariwal ◽  
...  
Keyword(s):  
Polymer Brushes ◽  
Mammalian Cells ◽  
Pore Formation ◽  
Multidrug Resistant ◽  
Membrane Pore ◽  
Threshold Size ◽  
Resistant Strains ◽  
Viable Approach ◽  
Nanoparticle Sizes

AbstractTo dissect the antibiotic role of nanostructures from chemical moieties belligerent to both bacterial and mammalian cells, here we show the antimicrobial activity and cytotoxicity of nanoparticle-pinched polymer brushes (NPPBs) consisting of chemically inert silica nanospheres of systematically varied diameters covalently grafted with hydrophilic polymer brushes that are non-toxic and non-bactericidal. Assembly of the hydrophilic polymers into nanostructured NPPBs doesn’t alter their amicability with mammalian cells, but it incurs a transformation of their antimicrobial potential against bacteria, including clinical multidrug-resistant strains, that depends critically on the nanoparticle sizes. The acquired antimicrobial potency intensifies with small nanoparticles but subsides quickly with large ones. We identify a threshold size (dsilica ~ 50 nm) only beneath which NPPBs remodel bacteria-mimicking membrane into 2D columnar phase, the epitome of membrane pore formation. This study illuminates nanoengineering as a viable approach to develop nanoantibiotics that kill bacteria upon contact yet remain nontoxic when engulfed by mammalian cells.

scholarly journals An Early Response to Environmental Stress Involves Regulation of OmpX and OmpF, Two Enterobacterial Outer Membrane Pore-Forming Proteins

2007 ◽  
Vol 51 (9) ◽  
pp. 3190-3198 ◽  
Author(s):  
Myrielle Dupont ◽  
Chloë E. James ◽  
Jacqueline Chevalier ◽  
Jean-Marie Pagès
Keyword(s):  
Outer Membrane ◽  
Early Response ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Membrane Pore ◽  
Bacterial Response ◽  
External Stresses ◽  
Resistant Strains ◽  
Pore Forming Proteins

ABSTRACT Bacterial adaptation to external stresses and toxic compounds is a key step in the emergence of multidrug-resistant strains that are a serious threat to human health. Although some of the proteins and regulators involved in antibiotic resistance mechanisms have been described, no information is available to date concerning the early bacterial response to external stresses. Here we report that the expression of ompX, encoding an outer membrane protein, is increased during early exposure to drugs or environmental stresses. At the same time, the level of ompF porin expression is noticeably affected. Because of the role of these proteins in membrane permeability, these data suggest that OmpF and OmpX are involved in the control of the penetration of antibiotics such as β-lactams and fluoroquinolones through the enterobacterial outer membrane. Consequently, the early control of ompX and ompF induced by external stresses may represent a preliminary response to antibiotics, thus triggering the initial bacterial line of defense against antibiotherapy.

scholarly journals The Biology and Role of Interleukin-32 in Tuberculosis

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Wu Li ◽  
Wanyan Deng ◽  
Jianping Xie
Keyword(s):  
Multidrug Resistant ◽  
Drug Resistant ◽  
Host Molecule ◽  
Tuberculosis Control ◽  
Promising Alternative ◽  
Extensively Drug Resistant ◽  
Important Host ◽  
Resistant Strains ◽  
Drug Resistant Strains

Tuberculosis, caused by Mycobacterium tuberculosis, remains a leading cause of morbidity and mortality globally, with nearly 10.4 million new cases of incidence and over 1.7 million deaths annually. Drug-resistant M. tuberculosis strains, especially multidrug-resistant or extensively drug-resistant strains, have further intensified the problem associated with tuberculosis control. Host-directed therapy is a promising alternative for tuberculosis control. IL-32 is increasingly recognized as an important host molecule against tuberculosis. In this review, we highlight the proinflammatory properties of IL-32 and the mode of action of IL-32 in mycobacterial infections to inspire the development of novel immunity-based countermeasures and host-directed therapies against tuberculosis.

The Epidemiology of Multidrug-ResistantAcinetobacter BaumanniiDoes the Community Represent a Reservoir?

2003 ◽  
Vol 24 (4) ◽  
pp. 275-279 ◽  
Author(s):  
Cosmina Zeana ◽  
Elaine Larson ◽  
Jyoti Sahni ◽  
S. J. Bayuga ◽  
Fann Wu ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Molecular Typing ◽  
Multidrug Resistant ◽  
Hospital Environment ◽  
Community Members ◽  
Community Residents ◽  
Potential Reservoir ◽  
Resistance Patterns ◽  
Resistant Strains

AbstractObjective:To explore the role of the community as a potential reservoir forAcinetobacter baumannii.Design:Antimicrobial resistance patterns and genotypes ofA. baumanniiisolates from patients in two Manhattan hospitals were compared with those ofA. baumanniiisolates from the hands of community members.Results:A total of 103 isolates from two hospitals (hospital A, 81; hospital B, 22) and 23 isolates from community residents were studied. Of the hospital isolates, 36.6% were multidrug resistant (hospital A, 68.2%; hospital B, 27.8%). In contrast, there were no multidrug-resistant isolates from the community (P< .005 between hospital and community). The prevalence ofA. baumanniion the hands of community residents was 10.4% (23 of 222). By molecular typing, 42 strains of A.baumanniiwere identified. Of the isolates from hospital A and hospital B, 55.6% (45 of 81) and 68.2% (15 of 22), respectively, were indistinguishable or closely related. In contrast, most community (83.3%) isolates were unrelated (P= .001 between hospital and community).Conclusion:Acinetobacterisolates from the community, characterized by a large variety of unrelated strains (83.3%), were distinct from the hospital isolates, of which 58.3% were closely related. The absence of multidrug-resistant strains in the community compared with 36.6% prevalence among hospital isolates suggests that the reservoir for epidemic strains resides in the hospital environment itself. To our knowledge, this is the first study to examine the community as a potential reservoir for hospital strains ofA. baumannii.

scholarly journals Non-pncAGene-Mutated but Pyrazinamide-Resistant Mycobacterium tuberculosis: Why Is That?

2017 ◽  
Vol 55 (6) ◽  
pp. 1920-1927 ◽  
Author(s):  
Jim Werngren ◽  
Erik Alm ◽  
Mikael Mansjö
Keyword(s):  
Susceptibility Testing ◽  
Gene Mutations ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Molecular Techniques ◽  
Content Type ◽  
Resistant Strains ◽  
Clear Majority

ABSTRACTPyrazinamide (PZA) is a key component for the effective treatment of drug-susceptible and PZA-susceptible multidrug-resistant (MDRPZA-S) tuberculosis (TB).pncAgene mutations are usually detected in a clear majority (>90%) of PZA-resistant strains but obviously not in all. Rapid and reliable PZA drug susceptibility testing (DST) is critical whenever PZA is to be used in a treatment regimen, not least for the treatment of MDRPZA-STB. In this study, we selected 26 PZA-resistant isolates reported to carry a wild-typepncAgene. To confirm resistance, susceptibility testing was repeated using 100 mg/liter and 200 mg/liter PZA for all the 26 isolates and Sanger sequencing was repeated on the 18 isolates that remained PZA resistant. Apart from the eight isolates initially misclassified as PZA resistant, the retests identified three factors responsible for the phenotype-genotype discrepancy:panDorrpsAmutations identified by whole-genome sequencing (WGS) (n= 7), heteroresistance (n= 8), and mixed populations withMycobacterium avium(n= 3). Additionally, we performed WGS on 400 PZA-susceptible isolates and 15 consecutive MDRPZA-Rclinical isolates. Of the 400 PZA-susceptible isolates, only 1 harbored a nonsynonymouspncAmutation (Thr87Met), whereas a nonsynonymousrpsAmutation was found in 17 isolates. None of these isolates carried a nonsynonymouspanDmutation, while all 15 of the MDRPZA-Risolates harbored a nonsynonymouspncAmutation. Our findings indicate that it is necessary to consider the occurrence ofpanDmutations in PZA-resistant isolates, as well as heteroresistance, for the development and evaluation of new molecular techniques to ensure high-quality DST performance. The identification of nonsynonymousrpsAmutations in both PZA-susceptible and PZA-resistant isolates also implies that further studies are needed in order to determine the role ofrpsAin PZA resistance.

scholarly journals Multiple introductions of multidrug-resistant typhoid associated with acute infection and asymptomatic carriage, Kenya

2021 ◽  
Author(s):  
Samuel Kariuki ◽  
Zoe A Dyson ◽  
Cecilia Mbae ◽  
Ronald Ngetich ◽  
Susan M Kavai ◽  
...  
Keyword(s):  
Informal Settlement ◽  
Acute Infection ◽  
Multidrug Resistant ◽  
Stool Culture ◽  
High Rate ◽  
Multiple Introductions ◽  
Resistant Strains ◽  
And Control ◽  
Control Study

AbstractUnderstanding the dynamics of infection and carriage of typhoid in endemic settings is critical to finding solutions to prevention and control. In a 3 year case-control study, we investigated typhoid among children aged <16 years (4,670 febrile cases and 8,549 age matched controls) living in an informal settlement, Nairobi, Kenya. 148 S. Typhi isolates from cases and 95 from controls (stool culture) were identified; a carriage frequency of 1%. Whole-genome sequencing showed 97% of cases and 88% of controls were genotype 4.3.1 (Haplotype58), with the majority of each (76% and 88%) being multidrug-resistant strains in 3 sublineages of H58 genotype (East Africa 1 (EA1), EA2, and EA3), with sequences from cases and carriers intermingled. The high rate of multidrug-resistant H58 S. Typhi, and the close phylogenetic relationships between carriers and controls, provides evidence for the role of carriers as a reservoir for the community spread of typhoid in this setting.

scholarly journals Helicobacter pylori antibiotic resistance and [13C]urea breath test values

2010 ◽  
Vol 59 (5) ◽  
pp. 588-591 ◽  
Author(s):  
Vincenzo De Francesco ◽  
Angelo Zullo ◽  
Federico Perna ◽  
Floriana Giorgio ◽  
Cesare Hassan ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Antibiotic Resistance ◽  
Breath Test ◽  
Multidrug Resistant ◽  
Urea Breath Test ◽  
Predictive Role ◽  
Resistant Strains ◽  
13C Urea Breath Test ◽  
H Pylori

A correlation between δ over baseline (DOB) values of the [13C]urea breath test (UBT) and Helicobacter pylori clarithromycin resistance has been reported, suggesting a possible predictive role of UBT in therapeutic outcome. However, available data are limited and conflicting. This study aimed to clarify this issue, assessing the possible relationship between H. pylori resistance towards different antibiotics (clarithromycin, metronidazole and levofloxacin) and UBT values. The data showed similar DOB values between susceptible and resistant strains for clarithromycin (46.9±32.3 vs 45.7±30.6; P=0.8), metronidazole (46.4±29.6 vs 47.4±37.9; P=0.8), and levofloxacin (45.0±30.2 vs 54.2±38.4; P=0.08). Likewise, comparable DOB values were observed between susceptible and multidrug-resistant strains (45.4±29.6 vs 54.8±44.8; P=0.1). In conclusion, our data failed to find a significant correlation between UBT values and H. pylori antibiotic resistance.

scholarly journals Multidrug-Resistant Campylobacer jejuni on Swine Processing at a Slaughterhouse in Eastern Spain

Animals ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1339
Author(s):  
Clara Marin ◽  
Laura Lorenzo-Rebenaque ◽  
Judith Moreno-Moliner ◽  
Sandra Sevilla-Navarro ◽  
Estefania Montero ◽  
...  
Keyword(s):  
Gastrointestinal Disease ◽  
Multidrug Resistant ◽  
Poultry Meat ◽  
Official Method ◽  
Control Programmes ◽  
Resistant Strains ◽  
High Level ◽  
Diffusion Assay ◽  
The Eu

Campylobacteriosis is the most commonly reported gastrointestinal disease in humans in the EU, mainly from poultry meat consumption. C. jejuni is the main species involved in the human disease. However, little is known about the role of swine meat in its epidemiology. Thus, the aim of this study was to assess the epidemiology and antimicrobial resistance of C. jejuni on swine processing at the slaughterhouse. To this end, a total of 21 pig herds were intensively sampled at the slaughterhouse. Campylobacter isolation was based on official method ISO 10272-1:2018, speciation was determined by the hippurate hydrolysis test, and antibiotic susceptibility was performed according to standard disc diffusion assay. The results showed that all batches shed Campylobacter in faeces upon arrival at the slaughterhouse and remained positive at the end of the slaughtering process (42.8%). Moreover, 41.5% of Campylobacter strains isolated were C. jejuni and all of them were resistant to at least one antibiotic, and 96.3% were multidrug-resistant strains. In conclusion, the high level of multidrug-resistant C. jejuni swine batch contamination at the slaughterhouse makes it necessary to include the swine sector in national control programmes to reduce the bacterium and its resistance.

scholarly journals Revising the Role of the Pneumococcal vex-vncRS Locus in Vancomycin Tolerance

2004 ◽  
Vol 186 (24) ◽  
pp. 8463-8471 ◽  
Author(s):  
Wolfgang Haas ◽  
Jack Sublett ◽  
Deepak Kaushal ◽  
Elaine I. Tuomanen
Keyword(s):  
Abc Transporter ◽  
Multidrug Resistant ◽  
Loss Of Function ◽  
Two Component System ◽  
Exact Function ◽  
Invasive Infections ◽  
Resistant Strains ◽  
Vancomycin Resistant ◽  
Vancomycin Treatment

ABSTRACT Vancomycin is used increasingly to treat invasive infections caused by multidrug-resistant Streptococcus pneumoniae. Although no vancomycin-resistant strains have been isolated to date, tolerant strains that fail to die rapidly and that cause relapsing disease have been described. The vex123-pep27 -vncRS locus, consisting of an ABC transporter, a presumed signaling peptide, and a two-component system, respectively, has been implicated in vancomycin tolerance. Recent findings, however, challenged this model. The data presented here indicate that erythromycin in the growth medium induces a vancomycin-tolerant phenotype and that loss of function of Pep27 or VncRS does not alter autolysis. However, a role for the ABC transporter encoded by the vex123 genes in tolerance was confirmed. A vex3 mutant was considerably more tolerant to vancomycin treatment than the wild-type strain T4, and the strength of the phenotype depended on the orientation of the resistance cassette used to construct the mutant. Microarray results suggested a number of genes that might be involved in tolerance in the vex3 mutant. Although the exact function and regulation of the vex123-pep27 -vncRS locus remains to be determined, several factors influence the autolysis behavior of S. pneumoniae, including the bacterial capsule, erythromycin, and the lytA and vex3 gene products.

scholarly journals Role of OmpA in the Multidrug Resistance Phenotype of Acinetobacter baumannii

2013 ◽  
Vol 58 (3) ◽  
pp. 1806-1808 ◽  
Author(s):  
Younes Smani ◽  
Anna Fàbrega ◽  
Ignasi Roca ◽  
Viviana Sánchez-Encinales ◽  
Jordi Vila ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Acinetobacter Baumannii ◽  
Protein A ◽  
Multidrug Resistant ◽  
Nosocomial Pathogen ◽  
Content Type ◽  
Resistance Phenotype ◽  
Resistant Strains ◽  
First Time

ABSTRACTAcinetobacter baumanniihas emerged as a nosocomial pathogen with an increased prevalence of multidrug-resistant strains. The role of the outer membrane protein A (OmpA) in antimicrobial resistance remains poorly understood. In this report, disruption of theompAgene led to decreased MICs of chloramphenicol, aztreonam, and nalidixic acid. We have characterized, for the first time, the contribution of OmpA in the antimicrobial resistance phenotype ofA. baumannii.

scholarly journals Evolution toward maximum transport capacity of the Ttg2 ABC system in Pseudomonas aeruginosa

2019 ◽  
Author(s):  
Daniel Yero ◽  
Lionel Costenaro ◽  
Oscar Conchillo-Solé ◽  
Mireia Díaz-Lobo ◽  
Adrià Mayo ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Outer Membrane ◽  
Gene Knockout ◽  
Multidrug Resistant ◽  
Crystallographic Structure ◽  
Intrinsic Resistance ◽  
Head Groups ◽  
Resistant Strains ◽  
System Thought

AbstractIn Pseudomonas aeruginosa, Ttg2D is the soluble periplasmic phospholipid-binding component of an ABC transport system thought to be involved in maintaining the asymmetry of the outer membrane. The crystallographic structure of Ttg2D at 2.5Å resolution reveals that this protein can bind two diacyl phospholipids. Native and denaturing mass spectrometry experiments confirm that Ttg2D binds two phospholipid molecules, which may have different head groups. Analysis of the available structures of Ttg2D orthologs allowed us to classify this protein family as a novel substrate-binding protein fold and to venture the evolutionary events that differentiated the orthologs binding one or two phospholipids. In addition, gene knockout experiments in P. aeruginosa PAO1 and multidrug-resistant strains show that disruption of this system leads to outer membrane permeabilization. This demonstrates the role of this system in low-level intrinsic resistance against certain antibiotics that use a lipid-mediated pathway to permeate through membranes.

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