Review articles
 

By Mr. Yadesh Prashad
Corresponding Author Mr. Yadesh Prashad
Windsor University School of Medicine, - United States of America
Submitting Author Mr. Yadesh Prashad
BACTERIOLOGY

Serratia Marcescens, S Marcescens, serratia, Marcescens, Serratia marcescens, Enterobacteriaceae

Prashad Y. A Critical Review of the Bacteria Serratia marcescens and its Impact on Human Health. WebmedCentral BACTERIOLOGY 2019;10(6):WMC005573

This is an open-access article distributed under the terms of the Creative Commons Attribution License(CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Submitted on: 27 Jun 2019 01:07:55 PM GMT
Published on: 27 Jun 2019 01:08:03 PM GMT

Abstract


Serratia marcescens is a gram negative bacterium of the family Enterobacteriaceae. Serratia marcescens is a motile opportunistic pathogen that produces the signature red pigment product prodigiosin. It possesses a thin cell membrane and thin peptidoglycan layer surrounded by an outer lipopolysaccharide (LPS) filled membrane. This saprophytic bacteria is able to withstand several different environmental conditions as it is a facultative anaerobe that can grow at temperatures ranging from 10ºC to 40ºC and at pH's ranging from 5 to 9 (Hejazi and Falkiner, 1997).

The Bacteria:


Serratia marcescens is a gram negative bacterium of the family Enterobacteriaceae. Serratia marcescens is a motile opportunistic pathogen that produces the signature red pigment product prodigiosin (See Figure 1). It possesses a thin cell membrane and thin peptidoglycan layer surrounded by an outer lipopolysaccharide (LPS) filled membrane. This saprophytic bacteria is able to withstand several different environmental conditions as it is a facultative anaerobe that can grow at temperatures ranging from 10ºC to 40ºC and at pH's ranging from 5 to 9 (Hejazi and Falkiner, 1997). It is due to these factors that S. marcescens is found in soil and water samples across many environments. Since this species of bacteria is able to thrive as a biofilm in aqueous environments or in its natural form in soil, it is also found in several species of plants, insects and animals. In addition to its natural existence in the environment, S. marcescens is a nosocomial pathogen that thrives in hospital environments and environments where levels of water and food sanitation (Especially meats and breads) are low (Mahlen, 2011).

Being classified as a nosocomial pathogen indicates that S. marcescens is a strain of bacteria that is able to thrive and infect humans in a hospital. It is known to cause several respiratory diseases such as pneumonia, central nervous system diseases, urinary tract infections, and bloodstream and wound infections (See Table 1). This is an opportunistic pathogen that primarily targets individuals who are immunocompromised; however, the contraction of this pathogen by health care workers and by non-hospital community areas occurs. Infrequently the contraction of this pathogen occurs due to contaminated surgical equipment, where gastrointestinal and respiratory tract infections are most frequently observed (Pitout, 2007).

Source of Outbreaks:


During the early 1900's, the dangers of S. marcescens were unknown, thus use of the correct safety measures when using this species were not implemented. This species of bacteria produces a distinct "blood like" protein that scientists often used it as a molecular marker to trace bacterial processes. Unfortunately, in many cases these individuals were infected with the pathogen, some resulting in death. Although the information on S. marcescens has drastically increased over the past century, the outbreak and spread of this bacterium still occurs. One source that contributes to the spread of this pathogen is the contamination of surgical equipment. The physical structures of the surface (Pili and hydrophobicity) of S. marcescens allow it to optimally bind to several surfaces, including an abundance of plastic-based surgical equipment (Fleisch et al., 2002). This contributes to the spread of this pathogen to exposed individuals.

The other major source that contributes to the spread of this pathogen is the contamination of food or water sources generally due to unhygienic conditions. This species of bacteria is highly motile and able to withstand varying conditions. Without proper chlorination of water, this bacterium ultimately infects human populations. Infected meat products are also a source of infection to humans. These conditions are often seen in developing countries and therefore chances of outbreaks are highest in those areas (Hejazi and Falkiner, 1997). Although the chances of outbreak are high, the probability of transmission to a general population is low, therefore there has been no reported pandemic concerning S. marcescens. However, isolated epidemics have occurred often in hospital settings (Lewis et al., 1989) and more specifically, neonatal intensive care units (Cristina, 2019).

Mechanism of Infection:


The amount of reported S. marcescens induced diseases has drastically decreased as information on this species of bacteria has increased. There are many structural factors that contribute to and increase the virulence of this species of bacteria. One of these structures is the presence of multiple pili. These pili extend from the surface of the cell membrane and allow for this organism to adhere to many surfaces including epithelial cells. Another factor that increases the pathogenicity of this species is the presence of many hydrophobic groups on the cell surface exterior. This results in the bacteria having a greater partitioning effect in highly hydrophobic oil like substances. Specifically this also allows the bacteria to adhere more strongly to plastic structures such as catheters and other surgical equipment (Hejazi and Falkiner, 1997).

Another major factor that contributes to the pathogenicity of this species is the lipopolysaccharide (LPS) containing outer membrane. The LPS layer has two major roles relating to virulence in which the Lipid A subunit is responsible for endotoxin activity and the oligosaccharide side chain confers partial resistance to certain antibiotics. The introduction of S. marcescens Lipid A into the human body results in an immunologic response in which this foreign antigen interacts with monocytes and macrophages. These immune response cells secrete several cytokines, including different groups of the interleukin (IL) and family tumour necrosis factor alpha (TNF-a). This then causes the production of endogenous inflammatory mediators and stimulates cellular toll-like receptors. This eventually leads to an overly active immune response in which the activity of the host cell defences ultimately exhaust and kill the cell (Makimura et al., 2007).

Treatment:


Throughout the history of human infection involving S. marcescens, the use of several different antibiotics has been implemented to effectively kill this strain. Unfortunately the misuse of certain antibiotics has contributed to the resistance of this pathogen. S. marcescens has become resistant to many antibiotics such as penicillin and cephalosporin (See Table 2). This resistance has primarily occurred due to horizontal gene transfer, in which the uptake of a plasmid conferring antibiotic resistance is introduced into a genetically susceptible cell. Unfortunately, since the species of the donor DNA is not a limiting factor, preventing resistance is difficult to control. In addition to this genetically induced resistance, this strain contains an efflux pump and an LPS membrane layer that both effectively prevent foreign substances from entering the cell (Farrar and O'Dell, 1976).

While this species has gained resistance to several antibiotics, it is still susceptible to third-generation cephalosporins. Until the species developed resistance to gentamicin in the mid-1970s, aminoglycosides were the drug of choice for treatment. Coincident with the decline in use, aminoglycoside resistance has decreased by 6% amongst S. marcescens isolates (Lockhart, 2007). Additionally, this treatment causes damage to cell membrane integrity, as well as is nephrotoxic and ototoxic (Shakil et al., 2008). As a result, these agents are largely used in combination with other antibiotics. Fluoroquinolones were able to effectively inhibit this species growth by inhibiting DNA gyrase activity. This effectively led to the fragmentation of bacterial DNA as torsional strains cannot be relieved effectively (Fabrega et al., 2009). However, divergent rates of fluoroquinolone resistance have limited the use of these antibiotics in cases of serious infection. Fluoroquinolone administration has become restricted to uncomplicated infection at clinical sites where effective antibiotic concentrations are attainable and thus reduce the likelihood of development of resistance (Livermore, 1998).

Previously, third-generation cephalosporins (such as cefotaxime and ceftazidime) were the cornerstone of treatment. However, the recognition that S. marcescens can both engage in constitutive over-production of broad spectrum AmpC beta-lactamase as well as express a range of ESBLs, has reduced the use of third generation cephalosporins as empiric agents. The utilization of these agents in isolates with evidence of AmpC derepression is contentious. High-frequency selection of AmpC derepressed mutants is not commonly associated with S. marcescens. However, the likelihood of selection ultimately depends on the site of infection, bacterial population density, drugs availability at the site of infection and the condition of the patient. Thus, in urinary tract infections where the level of available antibiotic is sufficient and the potential for selection is reduced, the drug of choice remains third-generation cephalosporins, used solely or with aminoglycosides (Livermore,1998). More often, in isolates of S. marcescens with evidence of AmpC derepression and/or ESBL production, the drug of choice is the carbapenems, as they remain active against bacteria with high levels of AmpC and ESBLS (Harris, 2012). However, carbapenemase-mediated resistance has emerged, suggesting careful administration be advised (Cai, 2008). In isolated outbreaks and sporadic episodes, reports of chromosomal and plasmid-mediated carbapenemase production have occurred thus making carbapenem treatment reserved for serious infection. If the pattern of spread of multi-resistant carbapenemase is reflected in this pathogen, treatment options will be severely limited (Cai, 2008).

S. marcescens employs virulence factors such as prodigiosin, proteases, biofilm and its ability to swim and swarm, all of which are controlled by a mechanism of intercellular communication termed quorum sensing. Quorum sensing enables bacterial cells to monitor their numbers and respond by coordinating the expression of genes including virulence genes. Due to the S. marcescens high virulence and resistance, the risk of further development of additional antibiotic resistance is posed with administration of antibiotics during treatment. It is supposed that quorum sensing inhibition is one useful approach that can help in treating infections, without exerting stress on the growth of bacteria to avoid the evolution of antibiotic resistance (Abbas, 2018). Glyceryl trinitrate (GTN) is an anti-hypertensive that has anti-microbial properties (Abbas, 2016). GTN exerted antibiofilm activity against Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa and Candida albicans. Further, it has demonstrated inhibition of quorum sensing in Pseudomonas aeruginosa (Abbas 2016) as well as S. marcescens (Abbas, 2018). GTN demonstrated, by its ability to cause significant reduction in the production of the quorum-sensing regulated violacein pigment, a reduction in quorum sensing associated virulence factors. GTN showed a remarkable reduction in prodigiosin pigment (Figure 2), protease production (Figure 3), biofilm production and blocked swarming motility (Figure 4,5) (Abbas, 2018). An advantage of GTN treatment is that it is FDA approved which makes clinical application possible. As Serratia marcescens causes surgical wounds and urinary tract infections, GTN can be used topically or as a catheter lock solution, for catheter associated urinary tract infections (Galloway, 2012).

While these treatments are effective against individuals already afflicted by S. marcescens, prevention remains the greatest means of combating this pathogen. The best way to avoid any unintentional contact with this species is to ensure the proper sterilization and sanitation of equipment, location, food and water. A variety of disinfectants such as phenolic disinfectants, (1% sodium hypochlorite, 70% ethanol) or formaldehyde are all effective against S. marcescens and can effectively prevent residues of these bacteria from forming on surfaces. Equipment that is used in a hospital setting should also undergo autoclave treatment. Lastly, all food and water sources should be inspected regularly for any trace of bacterial contaminant. In addition to inspection, these products should be treated with appropriate sanitizing agents (Human Pathogen and Toxins Act, 2009).

Laboratory Use:


When working with different species of bacteria it is imperative to have a full understanding about the potential risks that these bacteria pose to humans. The Human Pathogens and Toxins Act (HPTA) aims to inform people of the potential risks associated with certain microorganisms by placing them into risk factor groups. Specifically the bacteria Serratia marcescens is classified into risk group two. To be considered group two risk factor, the organism must moderately threaten the health of an individual and pose a low threat to public health. The pathogen must further be able to potentially cause serious disease in a human, although this is fairly unlikely to occur. Treatment and preventative measures are available for these pathogens therefore the risk of contraction and spread is low (Human Pathogen and Toxins Act, 2009).

In addition to outlining the general risks of certain pathogens, the HPTA also outlines the conditions in which the general use and disposal of the pathogens must be applied. For pathogens such as Serratia marcescens that are categorized in risk group two, use of this organism must be conducted in a research, diagnostic or health services laboratory setting. These are open bench laboratories that often use a biological safety cabinet to dispose of aerosols. Good microbial techniques (GMT) are also practised along with the use of minimal protective clothing to reduce the chance of infection. To safely dispose of level two pathogens, both solid and liquid contaminants must be autoclaved or chemically disinfected (See Table 3). If genetically engineered organisms were created in the experiment, a registration document must be filed describing the nature of these organisms. While working with this species does impart a low risk of potential human infection, there are many accessible treatments to combat any possible infections. Therefore this strain of bacteria is often used as a model organism in specific studies (Human Pathogen and Toxins Act, 2009).

References:


  1. Fabrega, A., Madurga, S., Giralt, E., and Vila, J. 2009. Mechanism of action of and resistance to quinolones. Microbial biotechnology. 2: 40-61.
  2. Farrar, W. E., and O'Dell, N. M. 1976. β-Lactamases and Resistance to Penicillins and Cephalosporins in Serratia marcescens. Journal of Infectious Diseases. 134: 245-251.
  3. Fleisch, F., Zimmermann-Baer, U., Zbinden, R., Bischoff, G., Arlettaz, R., Waldvogel, K., & Christian, R. 2002. Three consecutive outbreaks of Serratia marcescens in a neonatal intensive care unit. Clinical infectious diseases. 34: 767-773.
  4. Hejazi, A., and Falkiner, F. R. 1997. Serratia marcescens. Journal of Medical Microbiology. 46: 903-912.
  5. Human Pathogens and Toxins Act (S.C. 2009, c. 24). Legislative Services Branch. Retrieved July 24th, 2014 from Department of Justice website:http://laws.justice.gc.ca/eng/acts/H- 5.67/FullText.html
  6. Lewis, A. M., Stephenson, J. R., Garner, J., Afshar, F., and Tabaqchali, S. 1989. A hospital outbreak of Serratia marcescens in neurosurgical patients. Epidemiology and infection. 102: 69-74.
  7. Mahlen, S. 2011. Serratia Infections: from Military Experiments to Current Practice. American Society for Microbiology.24: 755-791.
  8. Makimura, Y., Asai, Y., Sugiyama, A., and Ogawa, T. 2007. Chemical structure and immunobiological activity of lipid A from Serratia marcescens LPS. Journal of medical microbiology. 56: 1440-1446.
  9. Pitout, J.D. 2007. Enterobacteriaceae Producing ESBLs in the Community: Are They a Real Threat? Infect Med. 24:57-65.
  10. Shakil, S., Khan, R., Zarrilli, R., and Khan, A. U. 2008. Aminoglycosides versus bacteria - a description of the action, resistance mechanism, and nosocomial battleground. Journal of biomedical science. 15: 5-14.
  11. Miller, M B, and B L Bassler. "Quorum Sensing in Bacteria." Annual Review of Microbiology, U.S. National Library of Medicine, 2001, www.ncbi.nlm.nih.gov/pubmed/11544353.
  12. Abbas, Hisham A, and Ahmed M Elsherbini. "Silencing the Nosocomial Pathogen Serratia Marcescens by Glyceryl Trinitrate." African Health Sciences, vol. 18, no. 1, 2018, p. 1., doi:10.4314/ahs.v18i1.2.
  13. Abbas HA, Shaldam MA. Glyceryl trinitrate is a novel inhibitor of quorum sensing in Pseudomonas aeruginosa. African Health Sciences. 2016;16(4):1117-1125.
  14. Galloway WR, Hodgkinson JT, Bowden S, Welch M, Spring DR. Applications of small molecule activators and inhibitors of quorum sensing in Gram-negative bacteria. Trends in Microbiology. 2012;20:449-458.
  15. Cristina, Maria Luisa, et al. "Serratia Marcescens Infections in Neonatal Intensive Care Units (NICUs)." MDPI, Multidisciplinary Digital Publishing Institute, 20 Feb. 2019, www.mdpi.com/1660-4601/16/4/610/htm.
  16. Lockhart SR, Abramson MA, Beekmann SE, Gallagher G, Riedel S, Diekema DJ, Quinn JP, Doern GV. Antimicrobial resistance among Gram-negative bacilli causing infections in intensive care unit patients in the United States between 1993 and 2004. J Clin Microbiol 2007; 45: 3352-3359.
  17. Livermore DM. b-lactamases in laboratory and clinical resistance. Clin Microbiol Rev 1995; 8: 557-584
  18. Harris PN, Ferguson JK. Antibiotic therapy for inducible AmpC beta-lactamase-producing Gram-negative bacilli: what are the alternatives to carbapenems, quinolones and aminoglycosides? Int J Antimicrob Agents 2012; 40: 297-305.
  19. Cai JC, Zhou HW, Zhang R, Chen GX. Emergence of Serratia marcescens, Klebsiella pneumoniae, and Escherichia coliisolates possessing the plasmid-mediated carbapenem-hydrolyzing beta-lactamase KPC-2 in intensive care units of a Chinese hospital. Antimicrob Agents Chemother 2008; 52: 2014-2018.

Illustrations


Table 1: The following table illustrates the major diseases associated with the S. marcescens bacterium. Note that infections involving respiratory and urinary tracts are the most prevalent.

 

Table 2: The following table illustrates the resistant rates of S. marcescens to a variety of antimicrobial agents from 2000 – 2009. The numbers recorded indicate the percentage of the isolates that were found to be resistant.

Table 3: The following table illustrates the sanitation procedures used in two hospitals for various hospital instruments.

 

Figure 1: The figure above illustrates colonies of S. marcescens streaked onto a nutrient agar. Note the characteristic red appearance of the colonies.

 

 

Figure 2: The figure above illustrates inhibition of prodigiosin pigment of Serratia marcescens by GTN. *, significant P< 0.05

URL:

 https://www.ncbi.nlm.nih.gov/ pmc/articles/PMC6016988/figure/F5/

 

 

 

 

Figure 3: The figure above shows inhibition of protease production by the skim milk agar method.

URL:

https://www.ncbi.nlm.nih.gov/ pmc/articles/PMC6016988/figure/F6/

 

 

 

Figure 4: The figure above demonstrates inhibition of swimming motility by GTN. *, significant P< 0.05.

URL:

https://www.ncbi.nlm.nih.gov/ pmc/articles/PMC6016988/figure/F7/

 

 

 

Figure 5: The figure above shows inhibition of swarming motility by GTN. *, significant P< 0.05.

URL:

https://www.ncbi.nlm.nih.gov/ pmc/articles/PMC6016988/figure/F8/

 

 

 

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