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Recently, the first Neisseria gonorrhoeae strain (H041) that is highly resistant to the extended-spectrum cephalosporin (ESC) ceftriaxone, the last remaining option for empirical first-line treatment, was isolated.
Scientists performed a detailed characterization of H041, phenotypically and genetically, to confirm the finding, examine its antimicrobial resistance (AMR), and elucidate the resistance
mechanisms...
However, on Feb 13th 2011:
"Gonorrhea acquires a piece of human DNA.
First evidence of gene transfer from human host to bacterial pathogen offers new view of evolution, disease"
If a human cell and a bacterial cell met at a speed-dating event, they would never be expected to exchange phone numbers, much less genetic material. In more scientific terms, a direct transfer of DNA has never been recorded from humans to bacteria.
Until now. Northwestern Medicine researchers have discovered the first evidence of a human DNA fragment in a bacterial genome – in this case, Neisseria gonorrhoeae, the bacterium that causes gonorrhea. Further research showed the gene transfer appears to be a recent evolutionary
event.
The discovery offers insight into evolution as well as gonorrhea's nimble ability to continually adapt and survive in its human hosts. Gonorrhea, which is transmitted through sexual contact, is one of the oldest recorded diseases and one of a few exclusive to
humans.
"This has evolutionary significance because it shows you can take broad evolutionary steps when you're able to acquire these pieces of DNA," said study senior author Hank Seifert, professor of microbiology and immunology at Northwestern University Feinberg School of Medicine. "The bacterium is getting a genetic sequence from the very host it's infecting. That could have far reaching implications as far as how the bacteria can adapt to the
host."
It's known that gene transfer occurs between different bacteria and even between bacteria and yeast cells. "But human DNA to a bacterium is a very large jump," said lead author Mark Anderson, a postdoctoral fellow in microbiology. "This bacterium had to overcome several obstacles in order to acquire this DNA sequence."
The paper will be published Feb. 14 in the online journal mBio.
The finding suggests gonorrhea's ability to acquire DNA from its human host may enable it to develop new and different strains of itself. "But whether this particular event has provided an advantage for the gonorrhea bacterium, we don't know yet, " Seifert
said.
Every year an estimated 700,000 people in the United States and 50 million worldwide acquire gonorrhea. While the disease is curable with antibiotics, only one drug is now recommended for treatment because the disease developed resistance to previously used antibiotic options over the past four
decades.
Gonorrhea is a particularly serious disease for women. If left untreated, gonorrhea can lead to pelvic inflammatory disease, a painful condition that can cause sterility and ectopic pregnancy. In rare cases, men and women can develop a form of the disease that leaves the genital tract and enters the bloodstream, causing arthritis and endocarditis, an infection of the inner lining of the heart.
An ancient disease that sounds like gonorrhea is described in the Bible, noted Seifert, who has studied the disease for 28 years. Most of his research focuses on how the bacterium evades the human immune system by altering its appearance and modulating the action of white blood cells.
The gene transfer was discovered when the genomic sequences of several gonorrhea clinical isolates were determined at the Broad Institute in Cambridge, Mass. Three of the 14 isolates had a piece of DNA where the sequence of DNA bases (A's, T's, C's and G's) was identical to an L1 DNA element found in
humans.
In Seifert's Feinberg lab, Anderson sequenced the fragment to reconfirm it was indeed identical to the human one. He also showed that this human sequence is present in about 11 percent of the screened gonorrhea
isolates.
Anderson also screened the bacterium that causes meningitis, Neisseria meningitidis, and is very closely related to gonorrhea bacteria at the genetic level. There was no sign of the human fragment, suggesting the gene transfer is a recent evolutionary
event.
"The next step is to figure out what this piece of DNA is doing," Seifert said.
The research was sponsored by the National Institutes of Health.
Source
Northwestern University
And now back to the
subject:
...H041 was examined using seven species-confirmatory tests, antibiograms (30 antimicrobials), porB sequencing, N. gonorrhoeae multiantigen sequence typing (NG-MAST), multilocus sequence typing (MLST), and sequencing of ESC resistance determinants (penA, mtrR, penB, ponA, and pilQ). Transformation, using appropriate recipient strains, was performed to confirm the ESC resistance determinants. H041 was assigned to serovar Bpyust, MLST sequence type (ST) ST7363, and the new NG-MAST ST4220. H041 proved highly resistant to ceftriaxone (2 to 4 µg/ml, which is 4- to 8-fold higher than any previously described isolate) and all other cephalosporins, as well as most other antimicrobials tested. A new penA mosaic allele caused the ceftriaxone
resistance.
In conclusion, Neisseria gonorrhoeae has now shown its ability to also develop ceftriaxone resistance. Although the biological fitness of ceftriaxone resistance in N. gonorrhoeae remains unknown, Neisseria gonorrhoeae may soon become a true superbug, causing untreatable gonorrhea.
A reduction in the global gonorrhea burden by enhanced disease control activities, combined with wider strategies for general AMR control and enhanced understanding of the mechanisms of emergence and spread of AMR, which need to be monitored globally, and public health response plans for global (and national) perspectives are important. Ultimately, the development of new drugs for efficacious gonorrhea treatment is
necessary.
Authors
Makoto Ohnishi (1), Daniel Golparian (2), Ken Shimuta (1), Takeshi Saika (3), Shinji Hoshina (4), Kazuhiro Iwasaku (5), Shu-ichi Nakayama (1), Jo Kitawaki (5), and Magnus Unemo (2).
(1) National Institute of Infectious Diseases, Tokyo, Japan,
(2) Swedish Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden, (3) Mitsubishi Chemical Medience Corporation, Tokyo, Japan
(4) Hoshina Clinic, Kyoto, Japan
(5) the Kyoto Prefectural University of Medicine, Kyoto,
Japan.
Source
American Society For Microbiology
See also
CDC Outlines Growing Resistance of Gonorrhea to Treatment
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New data outlines urgent need for effective alternative drug treatments
Two cases of verified clinical failures using internationally recommended first-line cefixime for gonorrhoea treatment,
Norway, 2010
(MDN)
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