Aquatic bacteria reveal a common genetic link to a deadly human pathogen

In 1675, when Dutch self-taught scientist Antoni van Leeuwenhoek first used his homemade microscope to examine a drop of rainwater, he made a discovery that would have an immeasurable impact on human health centuries later. Replicating his observations with a lake, pond, well and seawater, Leeuwenhoek revealed “in every drop of water…an incredible world of life”, teeming with “living creatures…little animalcules”.1,2 Among living creatures were the first bacteria ever visualized, earning Leeuwenhoek the title of father of microbiology and starting a microbiological tale spanning centuries and the world.

Steven Djordjevic and his team characterized elizabethkingia from Australian aquatic samples.

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Nearly three hundred years later and an ocean away, American microbiologist Elizabeth O. King has been commissioned by the United States Centers for Disease Control and Prevention to characterize a new pathogen responsible for a deadly epidemic of meningitis – inflammation of the membranes surrounding the brain. She classified the bacteria from clinical samples and named it Flavobacterium meningosepticum,3 which was later renamed elizabethkingia meningoseptic in his honour.4 In the following decades, deadly elizabethkingia infections have emerged in healthcare facilities around the world5,6 due to contaminated water systems, equipment and medical devices.seven,8,9 elizabethkingia are now recognized as emerging, deadly opportunistic pathogens that cause antimicrobial-resistant infections, with bodies of water, such as those studied by Leeuwenhoek, acting as reservoirs.ten

Nearly 350 years after Leeuwenhoek first made eye contact with bacteria in a drop of water, Steven Djordjevic, a microbiologist at Australia University of Technology, and his team collected water samples dam, river and wetland, characterized the whole genome sequences of 94 elizabethkingia isolates from these aquatic environments and compared them to clinical strains from Australia and overseas to understand the implications for clinical transmission.11 In a study recently published in Current Research in Microbial Sciences,11 the researchers analyzed the genomes of these isolates, demonstrated the genetic relationships between elizabethkingia species from aquatic and clinical samples, and identified genetic elements that contribute to the spread of antimicrobial resistance.

Connect the branches of the phylogenetic tree

The researchers developed a phylogenetic tree – a branching diagram illustrating evolutionary relationships – which contained 148 elizabethkingia isolates: 94 local aquatic samples, 27 local clinical and hospital samples and 27 international strains from GenBank, a publicly available database. Overall, they classified the 148 isolates into seven phylogenetically distinct species, the most abundant of which were known human pathogens. Elizabethkingia miricola and Elizabethkingia anophelis. Among these, Djordjevic’s team identified a possible yet unknown and pathogenic species of elizabethkingiawhich they name Elizabeth kingia umeracha, who shared more than 60 disease-promoting genes with E. miricola and E. anophelis isolated. The genetic patterns of three E. anophelis isolates from the wetland and dam samples were closely related to several E. anophelis Australian hospital sink isolates12 and patients with antibiotic-resistant sepsis, indicating a potential route from the environment to the clinic.

Tracking the gene flow of antibiotic resistance

Researchers are using bacterial whole genome sequencing to compare the phylogenetic relationship between environmental and clinical samples.

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“Waterborne infections that are already resistant to our strongest antibiotics pose a real threat to human health. Maybe not on a large scale, but often the scale doesn’t matter to the person who has the elizabethkingia infection,” Djordjevic explained. Metallo-β-lactamases (MBLs) – bacterial enzymes that deactivate the most widely used β-lactam antibiotics – are among the mechanisms that bacteria exploit to confer antibiotic resistance. As the only organisms with three genes responsible for activating MBLs, elizabethkingia are naturally resistant to three main classes of antibiotics: carbapenems, β-lactams and cephalosporins. Djordjevic and his colleagues found that the 94 aquatic elizabethkingia samples transported these three genes, variants of which were present in several elizabethkingia species highly resistant to β-lactams and other clinically important last-line antibiotics. Other isolates were even more resistant to other classes of antibiotics, suggesting that the bacteria use novel antimicrobial resistance processes.

Djordjevic and his team also found that 71% of 94 elizabethkingia the environmental samples contained specific mobile genetic elements (MGEs) – genetic material that moves within or between genomes – that allow the spread of antibiotic resistance. MGEs carrying resistance genes can integrate into the chromosomes of novel bacterial hosts and create antibiotic resistant phenotypes,13 that contribute to emerging and ongoing pathogenesis in infected humans. This finding represents an important direction for future research on mitigating emerging pathogenesis. Erica Donner, an environmental scientist at the University of South Australia who co-authored the study, said “environmental sites may act as potential sources of future outbreak clones and [clinically challenging] genes can quietly lurk all around us, just waiting for the opportunity and the encouragement through selective pressure to jump on a moving element and go rogue.

Breeding Success Strategies

Microbial communities in the 1600s have evolved significantly since Leeuwenhoek first observed his water samples. Daniel Jaén-Luchoro, an infectious disease researcher at the University of Gothenburg in Sweden, who was not involved in this work, stresses its importance in predicting “how resistance can be transmitted not only to strains of the same species , but also to other species. This knowledge is essential for designing strategies to prevent or control infections caused by these emerging pathogens. He explained that the widespread use of antimicrobials in clinical, aquaculture and agricultural settings leads to their accumulation in the environment through contamination of wastewater and agricultural runoff. As a result, environmental bacteria that have a natural resistance to antibiotics are exposed to strong selective pressure. This accelerates the evolution and spread of highly resistant strains, which thrive, transfer resistance genes to other strains, and eventually colonize humans.

According to Donner, “When we interrogate the environmental aspect of antimicrobial resistance, we begin to understand why we should do all we can to limit selection pressure to slow the evolution and spread of potentially deadly superbugs.” Understanding the genetic signatures of these species can inform prevention and treatment strategies. For example, positive clinical results in patients elizabethkingia infections depend on early diagnosis and antibiotic treatment that targets the pathogen’s unique resistance profile. Enhanced infection prevention strategies, such as disinfection, sink splash guards, and water purification, are also key to minimizing the spread of waterborne pathogens.

This study highlights the interconnectedness between us and the vast world of microbes we inhabit, providing evidence for possible shared origins between aquatic bacteria and those that cause fatal hospital-acquired infections. Leeuwenhoek led the way when he first used his microscope to examine water and find out what others had missed. The genomics technology used by Djordjevic and his team, including whole genome sequencing, allows scientists to peer ever deeper into the microbiological wonders of a single drop of water, reminding us that what we see depends on the instruments of perception. that we use.

References

  1. AV Leeuwenhoek, “Observations, communicated to the editor by M. Antony van Leewenhoek, in a Dutch letter of October 9th. 1676. English here’d: concerning the small animals by him observed in rain-well-sea- and snow-water; as also in the water where the pepper had been infused, ” Phil Trans R Soc, 12821–31, 1677.
  2. N. Lane, “The Unseen World: Reflections on Leeuwenhoek (1677) ‘Concerning Small Animals’,” Phil Trans R Soc B370:20140344, 2015.
  3. EO King et al., “Studies of a group of previously unclassified bacteria associated with meningitis in infants”, Am J Clin Pathol31(3):1, 241-247, 1959.
  4. KK Kim et al., “Transfer of Chryseobacterium meningosepticum and Chryseobacterium miricola to Elizabethkingia gen. nov. such as Elizabethkingia meningoseptica comb. nov. and Elizabethkingia miricola comb. nov.,” Int J Syst Evol Microbiol55(Pt 3):1287-93, 2005.
  5. EJ Dziuban et al., “elizabethkingia in children: a comprehensive review of symptomatic cases reported from 1944 to 2017,” Blink Infect Dis67(1):144–9, 2018.
  6. JT Kirby et al., “Antimicrobial susceptibility and epidemiology of a worldwide collection of Chryseobacterium spp: report of the SENTRY antimicrobial surveillance program (1997-2001)”, J Clin Microbiol42(1):445-8, 2004.
  7. MN Balm et al., “Bad design, bad practices, bad bugs: frustrations in controlling an outbreak of Elizabethkingia meningoseptica in intensive care units”, J Hosp Infect, 85(2):134-40, 2013.
  8. S. N. Hoque et al., “Chryseobacterium (Flavobacterium) meningosepticum outbreak associated with colonization of water taps in a neonatal intensive care unit,” J Hosp Infect, 47(3):188-92, 2001.
  9. YL Lee et al., “A dominant strain of Elizabethkingia anophelis emerged from a hospital water system to cause a three-year outbreak in a respiratory care center,” J Hosp Infect108:43-51, 2021.
  10. JF Bernardet et al., “The genera Chryseobacterium and Elizabethkingia”, ProkaryotesM. Dworkin et al., eds., New York: Springer, 7: 638-76, 2006.
  11. S. Hem et al, “Genomic analysis of elizabethkingia species in aquatic environments: evidence of potential clinical transmission”, Curr Res Microb Sci, 26;3:100083, 2021.
  12. D. Burnard et al., “Comparative genomics and antimicrobial resistance profiling of elizabethkingia reveal nosocomial transmission and in vitro sensitivity to fluoroquinolones, tetracyclines and trimethoprim-sulfamethoxazole”, J Clin Microbiol24;58(9):e00730-20, 2020.
  13. J. Davies et al., “Origins and evolution of antibiotic resistance”, Microbiol Mol Biol Rev74(3):417-33, 2010.

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