Tag Archives: Gram-positive bacteria

The World Health Organization (WHO) Ranks Worlds Most Deadliest “Superbugs” In the World

 

the WHO has ranked world’s most deadly “Superbugs” in the world:

Three bacteria were listed as critical:

  • Acinetobacter baumannii bacteria that are resistant to important antibiotics called carbapenems. These are highly drug resistant bacteria that can cause a range of infections for hospitalized patients, including pneumonia, wound, or blood infections.
  • Pseudomonas aeruginosa, which are resistant to carbapenems. These bacteria can cause skin rashes and ear infectious in healthy people but also severe blood infections and pneumonia when contracted by sick people in the hospital.
  • Enterobacteriaceae that are resistant to both carbepenems and another class of antibiotics, cephalosporins. This family of bacteria live in the human gut and includes bugs such as E. coli and Salmonella.

The list, which was released February 27th, 2017 and enumerates 12 bacterial threats, grouping them into three categories: critical, high, and medium.

“Antibiotic resistance is growing and we are running out of treatment options. If we leave it to market forces alone, the new antibiotics we most urgently need are not going to be developed in time,” said Dr. Marie-Paule Kieny, the WHO’s assistant director-general for health systems and innovation.

The international team of experts who drew up the new list urged researchers and pharmaceutical companies to focus their efforts on a type of bacteria known as Gram negatives.

(The terminology relates to how the bacteria respond to a stain — developed by Hans Christian Gram — used to make them easier to see under a microscope.)

Dr. Nicola Magrini, a scientist with the WHO’s department of innovation, access and use of essential medicines, said pharmaceutical companies have recently spent more efforts trying to find antibiotics for Gram positive bacteria, perhaps because they are easier and less costly to develop.

Gram negative bacteria typically live in the human gut, which means when they cause illness it can be serious bloodstream infections or urinary tract infections.

Gram positive bacteria are generally found outside the body, on the skin or in the nostrils.

Kieny said the 12 bacteria featured on the priority list were chosen based on the level of drug resistance that already exists for each, the numbers of deaths they cause, the frequency with which people become infected with them outside of hospitals, and the burden these infections place on health care systems.

Paradoxically, though, she and colleagues from the WHO could not provide an estimate of the annual number of deaths attributable to antibiotic-resistant infections. The international disease code system does not currently include a code for antibiotic-resistant infections; it is being amended to include one.

Six (6) others were listed as high priority for new antibiotics. That grouping represents bacteria that cause a large number of infections in otherwise healthy people. Included there is the bacteria that causes gonorrhea, for which there are almost no remaining effective treatments.

Three (3)  other bacteria were listed as being of medium priority, because they are becoming increasingly resistant to available drugs. This group includes Streptococcus pneumoniae that is not susceptible to penicillin. This bacterium causes pneumonia, ear and sinus infections, as well as meningitis and blood infections.

The creation of the list was applauded by others working to combat the rise of antibiotic resistance.

“This priority pathogens list, developed with input from across our community, is important to steer research in the race against drug resistant infection — one of the greatest threats to modern health,” said Tim Jinks, head of drug-resistant infections for the British medical charity Wellcome Trust.

“Within a generation, without new antibiotics, deaths from drug-resistant infection could reach 10 million a year. Without new medicines to treat deadly infection, lifesaving treatments like chemotherapy and organ transplant, and routine operations like caesareans and hip replacements, will be potentially fatal.”

FULL LIST:

Priority 1: Critical
1. Acinetobacter baumannii, carbapenem-resistant
2. Pseudomonas aeruginosa, carbapenem-resistant
3. Enterobacteriaceae, carbapenem-resistant, ESBL-producing

Priority 2: High
4. Enterococcus faecium, vancomycin-resistant
5. Staphylococcus aureus, methicillin-resistant, vancomycin-intermediate and resistant
6. Helicobacter pylori, clarithromycin-resistant
7. Campylobacter spp., fluoroquinolone-resistant
8. Salmonellae, fluoroquinolone-resistant
9. Neisseria gonorrhoeae, cephalosporin-resistant, fluoroquinolone-resistant

Priority 3: Medium
10. Streptococcus pneumoniae, penicillin-non-susceptible
11. Haemophilus influenzae, ampicillin-resistant
12. Shigella spp., fluoroquinolone-resistant

 

to read the article in its entirety click on the link below to be redirected:

http://www.businessinsider.com/the-who-has-ranked-the-deadliest-superbugs-in-the-world-2017-2

Clostridium difficile (C. diff. ) Research Community – December 2013

Here’s the latest from the Clostridium difficile research community:

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The 19.8kb Pathogenicity Locus or PaLoc of C.difficile expresses genes for the toxins as well as genes that regulate toxin production.  Additionally mobile genetic elements are also responsible for acquisition of antibiotic resistance genes.  Dingle et al. look at the evolutionary history of the mobile elements in C.difficile and suggest that PaLoc is mobilized rarely via homologous recombination, whereas Tn6218 is mobilized frequently through transposition.

http://gbe.oxfordjournals.org/content/early/2013/12/11/gbe.evt204.long

 

Toxin regulation may also be controlled by additional genes other than the usual suspects present on the PaLoc such as flagella.  In B. subtilis, the sigma factor SigD controls flagellar synthesis, motility, therefore it is possible that a homolog of SigD present in the C.difficile 630 genome could also control toxin production.  A sigD mutant in C. difficile 630 ∆erm displayed decreased expression of genes involved in flagellar biosynthesis, and also of genes encoding TcdA and TcdB as well as TcdR, the positive regulator of the toxins. Thus, SigD appears to be the first positive regulator of the toxin synthesis via direct control of tcdR transcription in C. difficile

 http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0083748

 

C. difficile is present in 60-70% of newborns and infantsIt has been speculated that newborns and infants lack the receptors for the disease-causing toxins secreted by C.difficile, and hence, are colonized, but remain disease-free. Alderbeth et al looked at the long term persistence of C.difficile in healthy infants from birth to ≥12 months of age.  Carriage of toxin producing genes was also characterized. Most strains (71%) were toxin producers, and 51% belonged to the 001 or 014 ribotypes, which often cause disease in adults. Toxin-producing strains colonizing young children for long time periods may represent a reservoir for strains causing disease in adults.

http://jcm.asm.org/content/52/1/173.long

 

With the emergence of a hypervirulent strain of C. difficile (BI/NAP1/027), the epidemiology of C. difficile infection has rapidly changed in the last decade.  In addition to toxin A and toxin B, hypervirulent strains produce a third toxin, binary toxin.  Although it has been speculated that binary toxin has an additive effect to damage already caused by the other two toxins, Kuehne et al created knock out  combinations of isogenic toxin mutants of R20291 and assessed their virulence in hamsters. They reconfirm their previous findings where they show either toxin A or toxin B alone can cause fulminant disease in the hamster infection model. In addition they show that in a double toxin mutant (ABC+; ie, an isogenic mutant producing only CDT), 3 of 9 animals succumbed to disease, although symptoms vary from those typically associated with C.difficile infection. Signs of wet tail, hemorrhage and inflammation in their small intestines were observed, thus suggesting an independent role of CDT in causing disease.

http://jid.oxfordjournals.org/content/209/1/83.long

 

For the first time the emergence of a hypervirulent strain of C. difficile (BI/NAP1/027) has been reported in China.

http://www.jstor.org/discover/10.1086/674405?uid=33374&uid=3739832&uid=2131&uid=2&uid=70&uid=3&uid=33372&uid=67&uid=62&uid=3739256&sid=21103168613797

 

Type IV pili are non-covalently assembled appendages, characterized now in both Gram-negative and Gram-positive bacteria. Peipenbrink et al show that C. difficile produces Type IV pili containing PilJ, a pilin with a novel dual-pilin fold. According to the suggested model, the C-terminal pilin domain is exposed in pili, providing a unique interaction surface. The novel fold of PilJ suggests a new mode for Type IV pilus function.

http://www.jbc.org/content/early/2013/12/21/jbc.M113.534404.long

 

Fecal microbiota transplantation (FMT) has been suggested as a new treatment to manage Clostridium difficile infection (CDI). Lofgren et al use a mathematical model of C. difficile within an intensive care unit (ICU), to examine the potential impact of routine FMT.  Results of this study suggest that the routine use of FMT represents a promising approach to reduce complex recurrent cases, but a reduction in CDI incidence will require the use of other methods to prevent transmission.

http://www.jstor.org/discover/10.1086/674394?uid=33374&uid=3739832&uid=2131&uid=2&uid=70&uid=3&uid=33372&uid=67&uid=62&uid=3739256&sid=21103168877297