You may think it would be impossible to get an infection in a sterile hospital operating room. However, not only is it possible, it's common for infections like those from a hospital, to be a part of an antibiotic resistant strain of bacteria. Multidrug-resistant Pseudomonas aeruginosa caused about 32,600 infections in hospitalized patients and 2,700 deaths in the United States in 2017. Hospitalized patients are most at risk, especially those on ventilators, with devices like catheters, and with wounds from burns or surgery [1]. Hospital-acquired infections and the pathogens responsible are a growing problem due to antibiotic resistance. Hospital patients are often immunocompromised, and contaminated surfaces promote bacterial transfer to new patients, so this is a large concern [2].
Pseudomonas is a bacteria typically found in the environment, in soil and water. P. aeruginosa most commonly infects humans causing pneumonia (lung infection) as well as infection in the blood or other areas of the body post surgery. Pneumonia killed over 808,000 children under the age of 5 in 2017, which accounts for 15% of all deaths of children under 5 years. Adults over the age of 65 and people with preexisting health problems are also at-risk for pneumonia. This isn’t a rare bacteria; it requires our attention [3]. Pseudomonas have developed resistance against many antibiotic types and are therefore multidrug-resistant and pose an issue for a seemingly safe hospital environment [1].
P. aeruginosa can be spread through contaminated water or soil. Resistant strains can spread from one person to another through contaminated hands, surfaces, or equipment. Patients and caretakers can avoid infection by washing hands to avoid getting sick and to avoid spreading germs as well as regular cleaning of rooms in a healthcare facility. Water management plans should also be in place to reduce exposure risk, however it can be difficult to thoroughly prevent infection [1].
P. aeruginosa is generally treated with antibiotics; however, with the increasing antibiotic resistance, this makes it difficult to treat. To find the best antibiotic for treatment, a culture needs to be sent to the lab to test which bacteria is active and grows against the antibiotics in order to find an antibiotic that will work. Since P. aeruginosa is multidrug-resistant, there are a limited number of treatment options [1].
P. aeruginosa is a threat in both healthcare and industrial biofouling, the bioincrustation or contamination of pipes and surfaces underwater. The surface attachment of this bacteria creates a problem for us because surface association induces virulence and is crucial in biofilm formation, which hampers antibiotic treatments we may use. Individual surface-attached P. aeruginosa does not have any known factors that allow its dispersal or spreading. However, in a study called “Pseudomonas aeruginosa detachment from surfaces via a self-made molecule” [2], a quantitative single-cell surface-dispersal assay is created and used to show that P. aeruginosa produces factors that can stimulate its own dispersal allowing it to live in many environments and efficiently infect its host [2].
One factor made by P. aeruginosa to induce its own dispersal is 2-methyl-4-hydroxyquinoline (MHQ), an alkyl quinolone with previously unknown activity. While pure MHQ is identified as a small molecule factor made by P. aeruginosa inducing the bacteria’s own dispersal, natural P. aeruginosa dispersal activity requires additional factors. Other alkyl quinolones can act as antibiotics or membrane depolarizers, but MHQ lacks this antibiotic ability and known antibiotics do not induce dispersal. Initial surface attachment strongly induces P. aeruginosa virulence. To initiate surface-induced virulence, P. aeruginosa senses surfaces through Type IV pili (TFP), which are extracellular polymers that are able to extend and retract. Instead of acting as an antibiotic, MHQ is found to inhibit the activity of TFP potentially explaining how MHQ causes dispersal of P. aeruginosa from the surface. This disruption of surface attachment and TFP activity could be a powerful yet unexploited mechanism to combat P. aeruginosa pathogenesis, by reducing its tendency to grow on surfaces and by reducing the induction of its virulence mechanisms. This research identifies single-cell surface dispersal as a new activity of P. aeruginosa-produced small molecules, characterizes MHQ as a promising dispersal agent, and establishes TFP inhibition as a viable mechanism for P. aeruginosa dispersal [2].
The main findings of this study show that MHQ dispersal is not due to antibiotic activity or membrane depolarization. This is different from many other alkyl quinolones which mainly act as antibiotics. MHQ possesses activity on its own and can be used as a powerful dispersal agent. In the assay done in this experiment, 10 minutes of treatment with MHQ was enough to induce dispersal of P. aeruginosa. To test whether this dispersal was a result of antibiotic activity, 10 minute treatments were executed with known antibiotics with varieties of action mechanisms including novobiocin (replication inhibitor), tetracycline (translation inhibitor), trimethoprim (metabolism disruptor), CCCP (membrane polarity disruptor), and gentamicin (translation inhibitor). None of these treatments resulted in as much dispersal as MHQ [2].
Figure 4. MHC inhibits Type IV pilus (TFP) activity
Figure 4A above shows the dispersal activity for all treatments tested in the DISPEL assay against the mid-log OD600 P. aeruginosa cells. CCCP (the far right teal bar) was the only other treatment that resulted in any significant dispersal. MHQ (the far left pink bar) shows to be extremely significant in producing the highest dispersal activity. These results show that antibiotic activity is insufficient in causing dispersal of P. aeruginosa as well as showing that MHQ does not function as an antibiotic agent. Figure 4H shows that the fraction of cells with pilus events with MHQ (right pink bar) are greatly inhibited compared to the PBS control (left grey bar). This is extremely significant in showing that MHQ is able to allow P. aeruginosa dispersal by inhibition of TFP activity pilus events [2].
MHQ is established as a small molecule factor that is made at low concentrations by P. aeruginosa and is able to disperse surface-attached P. aeruginosa at high concentrations. Biofilms are known to be difficult to treat with conventional antibiotics, and MHQ could be beneficial in combating the initial formation of biofilms (surface adhesion). MHQ function is presented in this study for the first time as it was previously unknown, but has now been found to inhibit TFP dynamics. TFP inhibition is enough to explain MHQ activity as MHQ inhibits TFP-dependent twitching motility and vertical surface attachment. It is suggested that MHQ can be useful for affecting other TFP-dependent behaviors beyond early surface attachment [2].
Since MHQ is made by P. aeruginosa, it is able to inhibit TFP surface attachment properties to therefore allow P. aeruginosa self-dispersal. The authors mention an interest in determining the specific mechanism of how MHQ disrupts TFP activity in the future to further understand the mechanics behind these findings [2]. Although, understanding the nitty-gritty details of P. aeruginosa dispersal seems unimportant, it is extremely beneficial; this bacteria is not inconsequential. P. aeruginosa plays a huge role in pneumonia and therefore many horrible deaths every year. If scientists can understand its dispersal properties and work around its multidrug antibiotic resistance by disrupting biofilm formation, many lives will be saved.
About the author:
Riley Hicks ‘21 is a Biology major and a Spanish minor at Mount Holyoke College. She is a two-year captain of the Swimming & Diving team, a three year Student Athletic Advisory Committee member and Vice-chair senior year, and she also works as a Spanish tutor and lifeguard. You can always find Riley on Skinner Green in her hammock with her friends or studying in Kendade.
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