Tata Value Homes Limited (TVHL), a 100% subsidiary of Tata Housing Development Company Limited, today strengthened its presence in South India by developing Spanish themed residential township at Sriperumbudur, near Chennai. The company plans to Invest around Rs 300 crore in setting up this township. Inspired by Spanish living, Santorini is designed by architects F+A. The township is spread across lush greenery at Sriperumbudur, one of the fastest growing corridors in Chennai. Speaking on the project Brotin Banerjee, MD & CEO, Tata Housing Development Co. Ltd., said, with rapid urbanisation and influx of global lifestyle trends more and more affluent home buyers are looking for homes to reflect the financial […]

ABSTRACT

Transporters belonging to the chromosomally encoded resistance-nodulation-division (RND) superfamily mediate multidrug resistance in Gram-negative bacteria. However, the cotransfer of large gene clusters encoding RND-type pumps from the chromosome to a plasmid appears infrequent, and no plasmid-mediated RND efflux pump gene cluster has yet been found to confer resistance to tigecycline. Here, we identified a novel RND efflux pump gene cluster, designated tmexCD1-toprJ1, on plasmids from five pandrug-resistant Klebsiella pneumoniae isolates of animal origin. TMexCD1-TOprJ1 increased (by 4- to 32-fold) the MICs of tetracyclines (including tigecycline and eravacycline), quinolones, cephalosporins, and aminoglycosides for K. pneumoniae, Escherichia coli, and Salmonella. TMexCD1-TOprJ1 is closely related (64.5% to 77.8% amino acid identity) to the MexCD-OprJ efflux pump encoded on the chromosome of Pseudomonas aeruginosa. In an IncFIA plasmid, pHNAH8I, the tmexCD1-toprJ1 gene cluster lies adjacent to two genes encoding site-specific integrases, which may have been responsible for its acquisition. Expression of TMexCD1-TOprJ1 in E. coli resulted in increased tigecycline efflux and in K. pneumoniae negated the efficacy of tigecycline in an in vivo infection model. Expression of TMexCD1-TOprJ1 reduced the growth of E. coli and Salmonella but not K. pneumoniae. tmexCD1-toprJ1-positive Enterobacteriaceae isolates were rare in humans (0.08%) but more common in chicken fecal (14.3%) and retail meat (3.4%) samples. Plasmid-borne tmexCD1-toprJ1-like gene clusters were identified in sequences in GenBank from Enterobacteriaceae and Pseudomonas strains from multiple continents. The possibility of further global dissemination of the tmexCD1-toprJ1 gene cluster and its analogues in Enterobacteriaceae via plasmids may be an important consideration for public health planning.

IMPORTANCE In an era of increasing concerns about antimicrobial resistance, tigecycline is likely to have a critically important role in the treatment of carbapenem-resistant Enterobacteriaceae, the most problematic pathogens in human clinical settings—especially carbapenem-resistant K. pneumoniae. Here, we identified a new plasmid-borne RND-type tigecycline resistance determinant, TMexCD1-TOprJ1, which is widespread among K. pneumoniae isolates from food animals. tmexCD1-toprJ1 appears to have originated from the chromosome of a Pseudomonas species and may have been transferred onto plasmids by adjacent site-specific integrases. Although tmexCD1-toprJ1 still appears to be rare in human clinical isolates, considering the transferability of the tmexCD1-toprJ1 gene cluster and the broad substrate spectrum of TMexCD1-TOprJ1, further dissemination of this mobile tigecycline resistance determinant is possible. Therefore, from a "One Health" perspective, measures are urgently needed to monitor and control its further spread. The current low prevalence in human clinical isolates provides a precious time window to design and implement measures to tackle this.

ABSTRACT

In Gram-negative bacteria, the permeability of the outer membrane governs rates of antibiotic uptake and thus the efficacy of antimicrobial treatment. Hydrophilic drugs like β-lactam antibiotics depend on diffusion through pore-forming outer membrane proteins to reach their intracellular targets. In this study, we investigated the distribution of porin genes in more than 2,700 Klebsiella isolates and found a widespread loss of OmpK35 functionality, particularly in those strains isolated from clinical environments. Using a defined set of outer-membrane-remodeled mutants, the major porin OmpK35 was shown to be largely responsible for β-lactam permeation. Sequence similarity network analysis characterized the porin protein subfamilies and led to discovery of a new porin family member, OmpK38. Structure-based comparisons of OmpK35, OmpK36, OmpK37, OmpK38, and PhoE showed near-identical pore frameworks but defining differences in the sequence characteristics of the extracellular loops. Antibiotic sensitivity profiles of isogenic Klebsiella pneumoniae strains, each expressing a different porin as its dominant pore, revealed striking differences in the antibiotic permeability characteristics of each channel in a physiological context. Since K. pneumoniae is a nosocomial pathogen with high rates of antimicrobial resistance and concurrent mortality, these experiments elucidate the role of porins in conferring specific drug-resistant phenotypes in a global context, informing future research to combat antimicrobial resistance in K. pneumoniae.

IMPORTANCE Klebsiella pneumoniae is a pathogen of humans with high rates of mortality and a recognized global rise in incidence of carbapenem-resistant K. pneumoniae (CRKP). The outer membrane of K. pneumoniae forms a permeability barrier that modulates the ability of antibiotics to reach their intracellular target. OmpK35, OmpK36, OmpK37, OmpK38, PhoE, and OmpK26 are porins in the outer membrane of K. pneumoniae, demonstrated here to have a causative relationship to drug resistance phenotypes in a physiological context. The data highlight that currently trialed combination treatments with a carbapenem and β-lactamase inhibitors could be effective on porin-deficient K. pneumoniae. Together with structural data, the results reveal the role of outer membrane proteome remodeling in antimicrobial resistance of K. pneumoniae and point to the role of extracellular loops, not channel parameters, in drug permeation. This significant finding warrants care in the development of phage therapies for K. pneumoniae infections, given the way porin expression will be modulated to confer phage-resistant—and collateral drug-resistant—phenotypes in K. pneumoniae.

Klebsiella species are problematic pathogens in neonatal units and may cause outbreaks, for which the sources of transmission may be challenging to elucidate. We describe the use of whole-genome sequencing (WGS) to investigate environmental sources of transmission during an outbreak of extended-spectrum-β-lactamase (ESBL)-producing Klebsiella michiganensis colonizing neonates. Ceftriaxone-resistant Klebsiella spp. isolated from neonates (or their mothers) and the hospital environment were included. Short-read sequencing (Illumina) and long-read sequencing (MinION; Oxford Nanopore Technologies) were used to confirm species taxonomy, to identify antimicrobial resistance genes, and to determine phylogenetic relationships using single-nucleotide polymorphism profiling. A total of 21 organisms (10 patient-derived isolates and 11 environmental isolates) were sequenced. Standard laboratory methods identified the outbreak strain as an ESBL-producing Klebsiella oxytoca, but taxonomic assignment from WGS data suggested closer identity to Klebsiella michiganensis. Strains isolated from multiple detergent-dispensing bottles were either identical or closely related by single-nucleotide polymorphism comparison. Detergent bottles contaminated by K. michiganensis had been used for washing milk expression equipment. No new cases were identified once the detergent bottles were removed. Environmental reservoirs may be an important source in outbreaks of multidrug-resistant organisms. WGS, in conjunction with traditional epidemiological investigation, can be instrumental in revealing routes of transmission and guiding infection control responses.

The IR Biotyper is a new automated typing system based on Fourier-transform infrared (FT-IR) spectroscopy that gives results within 4 h. We aimed (i) to use the IR Biotyper to retrospectively analyze an outbreak of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP) in a neonatal intensive care unit and to compare results to BOX-PCR and whole-genome sequencing (WGS) results as the gold standard and (ii) to assess how the cutoff values used to define clusters affect the discriminatory power of the IR Biotyper. The sample consisted of 18 isolates from 14 patients. Specimens were analyzed in the IR Biotyper using the default analysis settings, and spectra were analyzed using OPUS 7.5 software. The software contains a feature that automatically proposes a cutoff value to define clusters; the cutoff value defines up to which distance the spectra are considered to be in the same cluster. Based on FT-IR, the outbreak represented 1 dominant clone, 1 secondary clone, and several unrelated clones. FT-IR results, using the cutoff value generated by the accompanying software after 4 replicates, were concordant with WGS for all but 1 isolate. BOX-PCR was underdiscriminatory compared to the other two methods. Using the cutoff value generated after 12 replicates, the results of FT-IR and WGS were completely concordant. The IR Biotyper can achieve the same typeability and discriminatory power as genome-based methods. However, to attain this high performance requires either previous, strain-dependent knowledge about the optimal technical parameters to be used or validation by a second method.

PURPOSE

Online programs may help to engage patients in advance care planning in outpatient settings. We sought to implement an online advance care planning program, PREPARE (Prepare for Your Care; http://www.prepareforyourcare.org), at home and evaluate the changes in advance care planning engagement among patients attending outpatient clinics.

Background:

Historically, some chiropractors have been critical of vaccination, and this has been the subject of recent media attention in Canada. We explored the association between media attention and public dissemination of vaccination information on Canadian chiropractors’ websites.

In this study, the plasmid content of clinical and commensal strains was analyzed and compared. The replicon profile was similar in both populations, except for L, M, A/C, and N (detected only in clinical strains) and HI1 (only in commensal strains). Although I1 and F were the most frequent replicons, only IncI1, sequence type 12 (ST12) was associated with bla_CMY-2 in both populations. In contrast, the widespread resistant IncF plasmids were not linked to a single epidemic plasmid.

Hypervirulent Klebsiella pneumoniae strains are the major cause of liver abscesses throughout East Asia, and these strains are usually antibiotic susceptible. Recently, multidrug-resistant and hypervirulent (MDR-HV) K. pneumoniae strains have emerged due to hypervirulent strains acquiring antimicrobial resistance determinants or the transfer of a virulence plasmid into a classic MDR strain. In this study, we characterized the clinical and microbiological properties of K. pneumoniae liver abscess (KPLA) caused by MDR-HV strains in Taiwan. Patients with community onset KPLA were retrospectively identified at Taipei Veterans General Hospital during January 2013 to May 2018. Antimicrobial resistance mechanisms, capsular types, and sequence types were determined. MDR-HV strains and their parental antimicrobial-susceptible strains further underwent whole-genome sequencing (WGS) and in vivo mice lethality tests. Thirteen MDR-HV strains were identified from a total of 218 KPLA episodes. MDR-HV strains resulted in similar outcomes to antimicrobial-susceptible strains. All MDR-HV strains were traditional hypervirulent clones carrying virulence capsular types. The major resistance mechanisms were the overexpression of efflux pumps and/or the acquisition of ESBL or AmpC β-lactamase genes. WGS revealed that two hypervirulent strains had evolved to an MDR phenotype due to mutation in the ramR gene and the acquisition of an SHV-12-bearing plasmid, respectively. Both these MDR-HV strains retained high virulence compared to their parental strains. The spread of MDR-HV K. pneumoniae strains in the community raises significant public concerns, and measures should be taken to prevent the further acquisition of carbapenemase and other resistance genes among these strains in order to avoid the occurrence of untreatable KPLA.

A fosfomycin-resistant and carbapenemase (OXA-48)-producing Klebsiella pneumoniae isolate was recovered, and whole-genome sequencing revealed ISEcp1-bla_CTX-M-14b tandemly inserted upstream of the chromosomally encoded lysR-fosA locus. Quantitative evaluation of the expression of lysR and fosA genes showed that this insertion brought a strong hybrid promoter leading to overexpression of the fosA gene, resulting in fosfomycin resistance. This work showed the concomitant acquisition of resistance to broad-spectrum cephalosporins and fosfomycin due to a single genetic event.

Plazomicin was tested against 697 recently acquired carbapenem-resistant Klebsiella pneumoniae isolates from the Great Lakes region of the United States. Plazomicin MIC₅₀ and MIC₉₀ values were 0.25 and 1 mg/liter, respectively; 680 isolates (97.6%) were susceptible (MICs of ≤2 mg/liter), 9 (1.3%) intermediate (MICs of 4 mg/liter), and 8 (1.1%) resistant (MICs of >32 mg/liter). Resistance was associated with rmtF-, rmtB-, or armA-encoded 16S rRNA methyltransferases in all except 1 isolate.

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Announcement comes as new report from Statistics Canada shows almost two million more Canadians have lost their jobs

The Government's new portal for arranging coronavirus tests has sparked confusion today, following a message suggesting home tests had run out by 9am.

But speaking at the daily Covid-19 Downing Street press conference, Mr Shapps revealed that there was popular demand for the test slots with 16,000 people registering on Friday morning alone. Around 5,000 also got home test kits. While around 46,000 had tried to apply through the site.

EXCLUSIVE

The National Lottery website is down due to a power failure, leaving users unable to check results or enter Wednesday's draw.

The emergency wage subsidy program is being extended beyond June, in an effort to encourage more employers to rehire staff and 'help kick-start' the gradual economic reopening, says Prime Minister Justin Trudeau in light of record-high job losses.

"You can select a regional test site drive-through appointment or home test kit.

Starting Monday, “park ambassadors” will be stationed at Ottawa’s busiest parks to provide information about what's permitted under pandemic rules.

We need to have a different strong, password for every website we go to. Password managers like Dashlane and 1Password help us remember them.

CoronaBuddy.co.uk helps connect people in need with local volunteers in their area

HAY FEVER is an allergic reaction to pollen. Expert nutritionist Hannah Braye details seven anti-inflammatory foods to include in your diet that may minimise symptoms.

After the better part of a year, Facebook has started rolling out its redesigned desktop website to all of its users. The company announced today it plans to complete the rollout over the "next few weeks." Moving forward, "The New Facebook" will be t...

"Do not sell my info" links popped up on websites New Year's Day as companies scrambled to comply with California's sweeping new consumer privacy protection law.

A website created by Google sister company Verily is screening people in the Bay Area for coronavirus testing, but telling anyone with symptoms they're not eligible. It's not the only mystery around the project.

It is one of the most popular and important websites for cattle producers, rangers and carbon farmers in northern Australia, but its funding is about to run out.

SunRice says it will guarantee Australian-grown rice returns to supermarkets in April if the Murray-Darling Basin Plan is changed so environmental water can be used to grow rice.

Postmedia Network Canada Corp. expects to qualify for at least $20.3 million in COVID-related emergency wage subsidies from the federal government, the owner of Canada's largest newspaper chain said Friday.

The federal government's emergency wage subsidy program, which is meant to help employers keep workers on the payroll, will be extended beyond its initial early June endpoint.

Connections allows users to post spare plane tickets and the name of the person the ticket is registered to in hopes of finding a traveler with the same name.

In the U.S. almost three quarters use it, along with others such as Instagram and Snapchat. Twenty-four per cent say they’re online almost constantly.

Health news and commentary from around the Web gathered by the ALLMedPage Today staff

Quest Diagnostics Incorporated and its subsidiary, Nichols Institute Diagnostics (NID), have entered into a global settlement with the United States to resolve criminal and civil claims concerning various types of diagnostic test kits that NID manufactured, marketed and sold to laboratories throughout the country until 2006. The payment of $302 million will resolve these allegations and represents one of the largest recoveries ever in a case involving a medical device.

Two subsidiaries of the Swedish company Trelleborg AB, one based in Virginia and the other in France, have agreed to plead guilty and pay a total of $11 million in criminal fines for their participation in separate conspiracies affecting the sales of marine products sold in the United States and elsewhere.

Bill Melot, a resident of Hobbs, N.M., appeared in federal court today before Magistrate Karen B. Molzen in Las Cruces, N.M., on tax and false statement charges. Melot, a farmer who owns approximately 250 acres in Lea County, N.M., was charged with tax evasion, failing to file tax returns, corruptly impeding the IRS, and making false statements to the U.S. Department of Agriculture.

The United States today sued Lincoln Fabrics Ltd., a Canadian company, and Lincoln Fabrics Inc., aka Lincoln Textiles Inc., its American subsidiary, under the False Claims Act in connection with the companies’ weaving and sale of defective Zylon fabric which was used as the key ballistic material in bullet-proof vests.

The department filed a lawsuit today in federal court for the Eastern District of Missouri alleging a pattern or practice of violations of the Fair Housing Act by the owner and managers of Forum Manor Apartments for refusing to rent to African-Americans and males, refusing to allow tenants to have African-American visitors, sexually harassing female tenants and retaliating against tenants who complained about such discrimination.

Lincoln Fabrics Ltd., a Canadian weaver of ballistic fabrics, and its American subsidiary, have agreed to pay the United States $4 million to settle the United States’ lawsuit against Lincoln for violations of the False Claims Act in connection with their role in the weaving of Zylon fabric used in the manufacture and sale of defective Zylon bullet-proof vests.

Parker ITR S.r.l. has agreed to plead guilty and to pay a $2.29 million criminal fine for participating in a conspiracy to rig bids, fix prices and allocate market shares of marine hose.

Ethex Corporation, a wholly owned subsidiary of St. Louis-based drug manufacturer, KV Pharmaceutical Company, pleaded guilty to two felonies and was sentenced today in connection with the manufacturing of oversized prescription drug tablets.

Two subsidiaries of American International Group Inc. have agreed to pay a minimum of $6.1 million to resolve allegations that they engaged in a pattern or practice of discrimination against African American borrowers.

Daimler AG, a German corporation, and three of its subsidiaries have resolved charges related to a Foreign Corrupt Practices Act (FCPA) investigation into the company’s worldwide sales practices.

Two subsidiaries of Exxon Mobil Corporation – Mobil Oil Guam Inc. and Mobil Oil Mariana Islands Inc. – have agreed to pay $2.4 million for allegedly violating the federal Clean Air Act by failing to control emissions from their facilities.

Bill Melot, a resident of Hobbs, N.M., was convicted today of tax evasion, failure to file tax returns, making false statements to the U.S. Department of Agriculture (USDA), and impeding the Internal Revenue Service (IRS) following a four day jury trial before Judge M. Christina Armijo in Albuquerque, N.M.

American pharmaceutical manufacturers Ortho-McNeil Pharmaceutical LLC and Ortho-McNeil-Janssen Pharmaceuticals Inc., both subsidiaries of Johnson & Johnson, have agreed to pay more than $81 million to resolve criminal and civil liability arising from the illegal promotion of the epilepsy drug Topamax.

A federal grand jury in San Francisco returned a superseding indictment against AU Optronics Corporation, its Houston-based American subsidiary and six of its executives for participating in a conspiracy to fix prices of TFT-LCD panels.

Univision Services Inc., a wholly-owned subsidiary of Univision Communications Inc., pleaded guilty today to one count of conspiracy to commit mail fraud in connection with a scheme to obtain increased radio broadcast time.

ABB Ltd’s U.S. subsidiary, ABB Inc., pleaded guilty to one count of violating the anti-bribery provisions of the FCPA and one count of conspiracy to violating these provisions of the FCPA. The court imposed a sentence that included a criminal fine of $17.1 million.