In November 2018, PLOS ONE attended the European Scientific Conference on Applied Infectious Disease Epidemiology (ESCAIDE) conference in Malta. The conference, which is organised annually by the European Centre for Disease Prevention and Control (ECDC),
Antibiotic resistance is often in the news, as it threatens the effectiveness of one of the foundations of modern medicine. Usually, the concern is about resistance that is inherent to the bacteria, or else develops in bacteria through genetic changes. A paper published today in PLOS ONE suggests another possibility.
In “Chemical communication of antibiotic resistance by a highly resistant subpopulation of bacterial cells,” authors Omar El-Halfawy and Miguel Valvano reveal that some species of bacteria may help others in surviving an antibiotic attack. In addition, they were able to provide insight into the mechanics of how the bacteria perform this action.
The study began with an observation of the bacterial species Burkholderia cenopecia, which typically grows in the soil but can infect people who have cystic fibrosis and those with compromised immune systems. The authors noted that a subpopulation of the species was more resistant to the antibiotic polymyxin B than other bacteria of the species. In other words, these resistant bacteria were more likely to survive after treatment with polymyxin B, and levels of antibiotics that killed the less resistant bacteria did not harm this (more resistant) subpopulation.
When the authors grew the more-resistant B. cenopecia with another strain of bacteria called Pseudomonas aeruginosa (a disease-causing bacterium that can co-exist with B. cenopecia), the P. aeruginosa were much more resistant to the antibiotic than when they grew in isolation.
Why might the P. aeruginosa be more resistant when they were in the presence of B. cenopecia?
The authors suspected that the B. cenopecia were releasing something into their environment that interfered with the action of the antibiotic, making it less potent. Experiments revealed that the bacteria were indeed secreting two proteins associated with increased antibiotic resistance: putrescine (named for its putrid odor!) and Ycel, a protein whose function was previously unknown.
The large amounts of secreted putrescine blocked the antibiotics’ binding to the surface of the bacteria, and could make both B. cenopecia and P.aeruginosa more resistant to polymyxin B when grown together.
Ycel, on the other hand, was able to bind to the antibiotic directly, presumably decreasing its potency. Ycel is predicted to bind amphiphilic molecules (such as detergents, which are attracted to both water and oil). Consistent with this prediction, the authors showed that Ycel had a protective effect against amphiphilic antibiotics and less of an effect against others.
These results have implications for combating the growing problem of antibiotic resistance. If we could prevent bacteria from making putrescine or Ycel, antibiotic treatments might be more effective, helping us eventually outflank resistance.
Citations: El-Halfawy OM, Valvano MA (2013) Chemical Communication of Antibiotic Resistance by a Highly Resistant Subpopulation of Bacterial Cells. PLoSONE 8(7): e68874. doi:10.1371/journal.pone.0068874
Bragonzi A, Farulla I, Paroni M, Twomey KB, Pirone L, et al. (2012) Modelling Co-Infection of the Cystic Fibrosis Lung by Pseudomonas aeruginosa and Burkholderia cenocepacia Reveals Influences on Biofilm Formation and Host Response. PLoS ONE 7(12): e52330. doi:10.1371/journal.pone.0052330
Images: Pseudomonas aeruginosa doi:10.1371/journal.pone.0066257
Humans interact with bacteria almost every minute of our lives. Of the millions of these interactions, only a handful result in disease, and some bacteria only cause infections under certain conditions. In a recent PLOS ONE study, researchers probe these healthy human-bacterial relations in one particularly notorious pathogen as it spends the majority of its time in our bodies, doing no harm.
Staphylococcus aureus can cause endocarditis, toxic shock syndrome and other diseases, killing approximately 1 in 100,000 infected people in the US each year. Strains like MRSA have also evolved to carry multiple antibiotic resistance genes, making infections extremely difficult to treat. If human-bacterial interactions are to be described as a ‘genetic arms race’, it may be tempting to cast S. aureus as an enemy that carries every available genetic weapon.
Yet despite a few sporadic skirmishes, the majority of our interactions remain peaceful, as these bacteria thrive in healthy human hosts. In fact, about a third of healthy adults carry S. aureus in our noses at some point in our lives. In the article, researchers analyzed the genetic changes in S. aureus carried in such hosts by sequencing the genomes of 130 strains of S. aureus from the nasal passages of 13 healthy adults, five of whom carried strains of MRSA (which is often harmless when carried nasally). Despite the arms race metaphors, they found that S. aureus strains in healthy hosts are not incessantly beefing up their genetic arsenal of antibiotic resistance or pathogenesis genes.
They found bacterial genomes were changed by processes of ‘micro-mutation’, i.e.: small bits of genetic material being added or removed, or changes in a single letter in the genetic code. Large insertions and deletions (macro-mutation) were also common, as were changes caused by bacteria-infecting viruses or small, independently moving rings of DNA called plasmids. Overall, the constant changes in S. aureus genomes were geared toward keeping bacterial genomes healthy by clearing erroneous or harmful mutations. Only on rare occasions did these bacteria acquire distinctive surface proteins or an enterotoxin that could alter their pathogenic potential. In addition, their research also analyzed changes in specific genes used to assess bacterial diversity and relatedness, and developed a new method to detect transmission of bacterial strains among human carriers. Read the full study to learn more about these interesting results.
Many of the changes identified in this study may not directly increase the virulence of disease-causing S. aureus. However, previous work by these researchers demonstrated that mutations arising in bacteria carried by healthy hosts may play an important role in tipping the balance between human health and disease. Here, the authors begin to paint a picture of what these mutations are and how they may occur.
Citation: Golubchik T, Batty EM, Miller RR, Farr H, Young BC, et al. (2013) Within-Host Evolution of Staphylococcus aureus during Asymptomatic Carriage. PLoS ONE 8(5): e61319. doi:10.1371/journal.pone.0061319
Image: Scanning electron micrograph of S.aureus with increased resistance to vancomycin. Credit CDC/ Matthew J. Arduino, DRPH
PLOS ONE is looking forward to connecting with our editors, authors, reviewers, and readers at the 113th General Meeting of the American Society for Microbiology in Denver, Colorado. Representing PLOS ONE will be Damian Pattinson, Executive Editor; Lindsay Kelley, Editorial Board Manager; Camron Assadi, Product Marketing Manager; and myself (Meg Byrne, Associate Editor).
PLOS ONE continues to publish many high-profile papers in microbiology. Some of the most highly cited articles published since 2011 include a genomic characterization of a deadly Escherichia coli strain; a “field guide” to more than 3000 isolates of methicillin-resistant Staphylococcus aureus found around the world; the genome sequence of a novel ammonia-oxidizing archaeon (a member of the recently discovered third domain of life); and an analysis of the lung microbiomes in smokers with chronic obstructive pulmonary disease, smokers without COPD, and non-smokers.
In the last month, a number of publications have caught our readers’ eyes. These include an article showing that a breast-milk protein can help fight antibiotic-resistant bacteria; a report of a new antibiotic developed from a bacteria-killing virus; a super-phylogeny of the over 3000 bacterial and archaeal genomes that have been sequenced to date; and an analysis of the immune response to a bacterial lung infection in a 500-year-old mummy.
Come find us at the meeting: We’d love to hear your thoughts about PLOS and science publishing, in general. We’ll be at booth #350 from Sunday, May 19th through Tuesday, May 21st.
For authors: Let us show you your article level metrics (ALMs) and give you a special author t-shirt. We can also show off one of our latest features, Relative Metrics (Beta), which allows you to compare your paper’s usage to the average usage of articles in related subject areas.
For prospective authors: Please come ask us any questions you have about publishing in PLOS ONE and the family of PLOS journals. We can enumerate the many advantages of publishing in our open access journals, including free readership rights, reuse and remixing rights, unrestricted copyright, automatic posting of the article, and machine accessibility of the published article.
For PLOS ONE academic editors: We are looking forward to seeing you at our Editorial Board Reception on Monday May 20th from 5:30 to 7:30 PM at the Hyatt Regency. We would love to fill you in on our plans for the future, get your feedback, and say a huge “Thank you!” It’s also a great opportunity to meet other academic editors. Please contact Lindsay Kelley or Camron Assadi for further information.
Also, PLOS Biology is looking forward to catching up with their academic editors at a “Meet the Editors” event on Sunday May 19th between 12:30 and 2:30 PM at the PLOS Booth.
We’re looking forward to seeing many microbiologists in Denver and discussing the small but mighty microbe.
Bacillus anthracis with the cell wall labelled red, the division septa labelled green, and the DNA labelled blue (Schuch et al. PLOS ONE 2013).
Blainey PC, Mosier AC, Potanina A, Francis CA, Quake SR (2011) Genome of a Low-Salinity Ammonia-Oxidizing Archaeon Determined by Single-Cell and Metagenomic Analysis. PLoS ONE 6(2): e16626. doi:10.1371/journal.pone.0016626
Corthals A, Koller A, Martin DW, Rieger R, Chen EI, et al. (2012) Detecting the Immune System Response of a 500 Year-Old Inca Mummy. PLoS ONE 7(7): e41244. doi:10.1371/journal.pone.0041244
Erb-Downward JR, Thompson DL, Han MK, Freeman CM, McCloskey L, et al. (2011) Analysis of the Lung Microbiome in the “Healthy” Smoker and in COPD. PLoS ONE 6(2): e16384. doi:10.1371/journal.pone.0016384
Lang JM, Darling AE, Eisen JA (2013) Phylogeny of Bacterial and Archaeal Genomes Using Conserved Genes: Supertrees and Supermatrices. PLoS ONE 8(4): e62510. doi:10.1371/journal.pone.0062510
Marks LR, Clementi EA, Hakansson AP (2013) Sensitization of Staphylococcus aureus to Methicillin and Other Antibiotics In Vitro and In Vivo in the Presence of HAMLET. PLoS ONE 8(5): e63158. doi:10.1371/journal.pone.0063158
Mellmann A, Harmsen D, Cummings CA, Zentz EB, Leopold SR, et al. (2011) Prospective Genomic Characterization of the German Enterohemorrhagic Escherichia coli O104:H4 Outbreak by Rapid Next Generation Sequencing Technology. PLoS ONE 6(7): e22751. doi:10.1371/journal.pone.0022751
Monecke S, Coombs G, Shore AC, Coleman DC, Akpaka P, et al. (2011) A Field Guide to Pandemic, Epidemic and Sporadic Clones of Methicillin-Resistant Staphylococcus aureus. PLoS ONE 6(4): e17936. doi:10.1371/journal.pone.0017936
Schuch R, Pelzek AJ, Raz A, Euler CW, Ryan PA, et al. (2013) Use of a Bacteriophage Lysin to Identify a Novel Target for Antimicrobial Development. PLoS ONE 8(4): e60754. doi:10.1371/journal.pone.0060754