Immuno-VIP and Immuno-CIP: a support in the effort to treat the urinary tract infections with bacteria and superbugs resistant to antibiotics

Immuno-VIP and Immuno-CIP: a support in the effort to treat the urinary tract infections with bacteria and superbugs resistant to antibiotics

The “superbug” Escherichia coli, multidrug resistant, including to the last-resort antibiotic colistin, showed up in China in 2015. The drug resistance gene known as mcr-1 – which has the capacity to move from one bacterium to another – was found in about 1% of E.coli bacteria and 1% of a bacteria known as Klebsiella pneumoniae, that can cause pneumonia, bloodstream infections, and wound infections. The mcr-1 gene confers transferable colistin resistance. Mcr-1-positive Enterobacteriaceae (MCRPE) has attracted substantial medical attention; the focus has been on the clinical aspects of mcr-1-positive Escherichia coli (MCRPEC) infection, and on the risk factors for MCRPEC carriage. Of 17,498 isolates associated with infection, mcr-1 was detected in 76 (~1%) of 5,332 E.coli isolates, 13 (<1%) of 348 Klebsiella pneumoniae, one (<1%) of 890 Enterobacter cloacae, and one (1%) of 162 Enterobacter aerogenes. Due to resistance to better antibiotics on the rise, Colistin had taken on increasing importance in medicine as a reserve antibiotic [1].

Acquired resistance due to chromosomal mutation and selection is termed vertical evolution, since the advantage will be conferred to a bacterial line. Bacteria also develops resistance through the acquisition of new genetic material from other resistant organisms through horizontal transfer; this may occur between strains of the same species or between different bacterial species or genera sharing a same ecological niche. Mechanisms of genetic exchange include conjugation, transduction, and transformation. For each of these processes, transposons facilitate the transfer and incorporation of the new resistance genes into the genome of the bacterial host or into plasmids [2].

Superbugs are present in Europe. Colistin-resistant E. coli was identified in pork meat [3]; Colistin-resistant Klebsiella pneumoniae strains were isolated from 18 patients in Romania, being included in the bacterial collection of the Faculty of Biology in Bucharest and in the germs collection of Activeimmunity.

Colistin resistance has been reported before, but not in this form. What makes this situation unique – and unsettling – is that the gene that makes the bacteria Colistin-resistant is contained in a plasmid, a mobile piece of DNA. Plasmids can easily move from one bacterium to another, both within the same family of bacteria and to other families, as well. That means E.coli carrying mcr-1 can share it with other E.coli, as well as pass it to bacteria like Klebsiella pneumoniae [5].

Bacteria found in humans, animals and food continue to show resistance to widely used antimicrobials, says the latest report on anti-microbial resistance (AMR) in bacteria by the European Food Safety Authority (EFSA) and the European Centre for Disease Prevention and Control (ECDC). The findings underline that AMR poses a serious threat to public and animal health. Infections caused by bacteria that are resistant to antimicrobials lead to about 25,000 deaths in the EU every year [6]. “Antimicrobial resistance is an alarming threat putting human and animal health in danger,” said Vytenis Andriukaitis, the EU’s health and food safety commissioner. “We have put substantial efforts to stop its rise, but this is not enough. We must be quicker, stronger and act on several fronts.” [7].

The emergence of multidrug resistant bacteria in urinary tract infections (UTIs) is a challenge to medical professionals. According to ECDC (2018), more than a third of K. pneumoniae and half of E. coli strains reported were resistant to at least one of the antibiotics under surveillance. Moreover, the emergence of Colistin resistance among Enterobacteriaceae leaves few therapeutic options against these ”superbugs”. Thus, chicken immunological active proteins (CIAP) have emerged as a potential supporting agent.

Chicken immunologically active proteins (CIAP) (egg proteins: IgY, holo-ovotransferrin, ovomucin, ovalbumin and lysozyme) were obtained from chickens immunized with antigens from Escherichia coli, Klebsiella pneumoniae, Enterococcus spp, Pseudomonas spp, Proteus spp, Candida spp, and MRSA strains. CIAP efficiency was demonstrated in vitro by: quantitative assay for Chicken IgY (ELISA Kit – ABCAM), rapid and slow agglutination test and bacterial growth inhibition test (HB&L ALIFAX, CIAP + live bacterial cultures).

References:

[1] Wang Y, Tian GB, Zhang R, Shen Y, Tyrrell JM, Huang X, Zhou H, Lei L, Li HY, Doi Y, Fang Y, Ren H, Zhong LL, Shen Z, Zeng KJ, Wang S, Liu JH, Wu C, Walsh TR, Shen J – Prevalence, risk factors, outcomes, and molecular epidemiology of mcr-1-positive Enterobacteriaceae in patients and healthy adults from China: an epidemiological and clinical study, Lancet Infect Dis, 2017, 17(4), 390–399;

[2]  Assessment of the Antibiotic Resistance Effects of Biocides, SCENIHR (Scientific Committee on Emerging and Newly Identified Health Risks), 2009, Accesed on line at: http://ec.europa.eu/ ;

[3] Sala C, Morar A, Morva AA – Antibiotic resistance of gram negative bacteria isolated from meat surface biofilm, Roum Biotech Lett, 2012, 17(4),7483-7492;

[4] *** Veterinary Medicines Division – Sales of veterinary antimicrobial agents in 25 EU/EEA countries in 2011. Third ESVAC report, 15 October 2013. EMA/236501/2013;

[5] Branswell H – Superbug resistant to last-resort antibiotics turns up in Europe, Stat, December 3, 2015, accessed: www.statnews.com/2015/12/03/superbug-antibiotics-europe/

[6] *** The European Union summary report on antimicrobial resistance in zoonotic and indicator bacteria from humans, animals and food in 2015, European Food Safety Authority. European Centre for Disease Prevention and Control, Adopted: 26 January 2017. doi: 10.2903/j.efsa.2017.469;

[7] Kelland K – “Alarming” superbugs a risk to people, animals and food, EU warns. Science News/ Wed Feb 22, 2017;

[8] Schaefer WB – Serologic identification and classification of the atypical mycobacteria by their agglutination, Am Rev Respir Dis. 1965, 92(6),85–93;

[9] Pătrașcu IV, Penescu M, Viasu L – Urinary tract infections (UTI) (2). Escherichia coli resistant to colistin and newly developed pathology, Romanian Academy Session, April 22, 2017 (in Romanian)

[10] Pătrașcu IV – Bio-prepared PC2 treatment, Romanian Academy Session Feb 27, 2015 (in Romanian).

[11] Treatment of urinary tract infections with antibiotic resistance bacteria and superbugs by Immuno-VIP and Immuno-CIP – Ionel Victor Pătraşcu, Liliana Viasu, Maria Serdaru, Ilies-Rares Preutu. 14th World Congress on Infection Prevention and Control (Theme: Novel Insights in Therapeutic Research on Infectious Diseases, Prevention and Control), December 6-7, 2018 Valencia, Spain

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