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Beschreibung

Pseudomonas aeruginosa is known as a persistent bacterial pathogen. Antibiotics are currently the most common bacterial treatment for related infections but cases of microbial resistance are on the rise. Toxin-Antitoxin Systems in Pseudomonas aeruginosa describes one of the most important antimicrobial targets in the bacterium species. The contributors have compiled comprehensive information on the subject. The reference initially acquaints the reader with key topics about P. aeruginosa infection including virulence factors, pathogenicity, epidemiology, laboratory diagnosis and antibiotic resistance. This is followed by detailed chapters on toxin-antitoxin systems which explain their role in the bacterial pathogenesis with reference to P. aeruginosa. The comprehensive information on the subject makes this an ideal reference for newcomers to the field of bacteriology and target discovery. Students of medical microbiology and medical professionals who are interested in the finer details of P. aeruginosa pathogenicity will also be equipped with sufficient information to join the discussion on this topic with fellow researchers.

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Table of Contents
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Disclaimer:
Limitation of Liability:
General:
FOREWORD
PREFACE
ACKNOWLEDGEMENTS
List of Contributors
An Overview of Pseudomonas aeruginosa
Abstract
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
History and Etymology
Abstract
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Virulence Factors of P. aeruginosa and Their Role in Pathogenicity
Abstract
1. Lipopolysaccharide (LPS)
2. Adhesions
2.1. Type IV Pili (TFP)
2.2. Lectins
2.3. Alginate
2.4. Flagella
3. PIGMENTS
3.1. Pyoverdine
3.2. Pyocyanin
3.3. Pyorubin
3.4. Pyomelanin
3.5. Other Pigments
4. P. aeruginosa forms in nature (planktonic and biofilm)
5. Toxins
5.1. Exotoxin A
5.2. Exotoxin S
5.3. Leukocidin (Cytotoxin)
5.4. Enterotoxin
6. Enzymes
6.1. Phospholipase C (PLC)
6.2. Rhamnolipid
6.3. Proteases
6.3.1. LasB
6.3.2. LasA
6.3.3. Alkaline Protease
6.3.4. Protease IV
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Epidemiology
Abstract
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Pathogenicity
Abstract
1. BACTEREMIA
2. Bone And Joint Infections
3. Keratitis
4. Pneumonia
5. Chronic Respiratory Tract Infections
6. Urinary Tract Infection (UTI)
7. Skin And Soft Tissues Infections
8. Ear Infections
9. Endocarditis
10. Central Nervous System (CNS) Infections
11. Enteric Infection
12. Mastitis
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Laboratory Diagnosis
Abstract
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Antibiotic Resistance and Treatment
Abstract
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Toxin-Antitoxin Systems
Abstract
1. CLASSIFICATION OF THE TA SYSTEMS
1.1. Type I TA System
1.2. Type II TA System
1.3. Type III TA System
1.4. Type IV TA System
1.5. Type V TA System
1.6. Type VI TA System
2. TA SYSTEM FUNCTIONS
2.1. Antibiotic Resistance
2.2. Biofilm Formation
2.3. Persister Cell Formation
2.4. Genomic Junk
2.5. Programmed Cell Death (PCD)
2.6. Post Segregational killing (PSK)
2.7. Plasmid Maintenance
2.8. Antiphage Activity
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Acquaintance with the Known Toxin-Antitoxin Systems in P. aeruginosa
Abstract
1. HIGBA TA SYSTEM
2. HICAB TA SYSTEM
3. PARDE TA SYSTEM
4. RELBE TA SYSTEM
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Toxin-Antitoxin Systems in Pseudomonas aeruginosa
Edited by
Mina Mahmoudi
Department of Microbiology
Faculty of Medicine
Ilam University of Medical Sciences
Iran
Sobhan Ghafourian
Department of Microbiology
Faculty of Medicine
Ilam University of Medical Sciences
Iran
&
Behzad Badakhsh
Department of Gastroenterology
Faculty of Medicine
Ilam University of Medical Sciences
Iran

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FOREWORD

Given the gap in the comprehensive book on Pseudomonas aeruginosa and the new findings, the authors decided to address as many important issues as possible about this bacterium. This book is also unique in novel information of P. aeruginosa. Still another factor is given by many interesting chapters in detail and plenty of colorful illustrations have been shown. After reading this book, it is hoped that the reader will acquire the necessary knowledge needed for treating patients and promoting useful research designs in eradicating bacteria. By knowing the pathogenesis pathways and new systems in this bacterium, a new horizon will be created in the reader's mind about this bacterium. Writing the book took about two years, with the help of prominent professors and researchers of Ilam University of Medical Sciences, who have been named in different chapters. The authors recommend reading this book to researchers and readers who are looking to solve medical problems in hospitals caused by this bacterium. It is hoped that reading this book will add useful information to readers. In my opinion, the authors would be pleased of having grateful readers who gain broad knowledge for their current practice in Microbiology and Infectious Disease and it will also provide help for their future research.

Mohammad Mehdi Feizabadi Department of Microbiology Faculty of Medicine Tehran University of Medical Science Tehran

PREFACE

No one knows exactly when humans and pathogenic bacteria were encountered with each other. But since then, the war began over life and survival between them. During this time, both sides of the war tried to equip themselves with all their might. Throughout time, sometimes humans and sometimes pathogenic bacteria have been victorious, but the contention has not ended yet. However, some of these pathogenic bacteria are stubborn fighters and require much more attention and unfortunately, humans have been disarmed against some of them. Among them, Pseudomonas aeruginosa is the pathogen that poses a serious threat to human health. The spectrum of its pathogenesis is very wide. So, the infection can range from a simple superficial infection to a deadly infection. Regrettably, it is one of the most resistant bacteria on the planet, which makes it one of the most prominent and ruthless bacterial fighters.

The present book deals with P. aeruginosa and toxin-antitoxin systems in the novel way. This book is recommended not only for interested students but also for those who are interested in research in this field. Currently, P. aeruginosa is one of the most essential topics for researchers due to its high pathogenicity and severe antibiotic resistance. On the other hand, toxin-antitoxin systems are considered as one of the most potentially novel antimicrobial targets. In recent years, several scientists have studied the toxin-antitoxin systems in P. aeruginosa and their role in pathogenicity, which have also achieved valuable results. Therefore, we have attempted to acquaint the readers with the P. aeruginosa as well as one of its most precious therapeutic potentials. However, studies in this area are very rare and limited, but we have tried to provide comprehensive information to the readers.

The chapters of this book are designed in such a way that even readers who have no knowledge of the subject of this book can get acquainted with it throughout the book. Accordingly, the contents of the book have been categorized in three main parts.

First, P. aeruginosa has been introduced in different aspects. In this section, readers will become familiar with this microorganism by studying the structure, pathogenicity, antibiotic resistance, and other features of this bacterium. It allows the readers to have almost complete information about the P. aeruginosa. Second, classification, structures and roles of toxin antitoxin systems in pathogenicity are explained, which determines how they are involved in the gene regulation and pathogenicity of the bacteria. Therefore, the reader will understand the importance and necessity of recognizing these systems. Third, well-known toxin-antitoxin systems and their functions have been discussed in P. aeruginosa. Indeed, we tried to provide useful information in an explicit way. At the end of the book, we hope that the readers will be almost ready to join other researchers by the approximate dominance to the topic. In addition, we look forward to be able to make a contribution to the advancement of science in this area.

Mina Mahmoudi Department of Microbiology Faculty of Medicine Ilam University of Medical Sciences IranSobhan Ghafourian Department of Microbiology Faculty of Medicine Ilam University of Medical Sciences Iran &Behzad Badakhsh Department of Gastroenterology Faculty of Medicine

ACKNOWLEDGEMENTS

We would like to express our deepest gratitude to God almighty for benefitting us with his kindness and support at all times. He gave us an opportunity to flourish and allowed us to be immersed in his unique molecular world, the blessings that only a few humans have benefited from.

We humbly extend thanks to our families for the patience and kindness that they showed at the time of writing this book.

We would like to express our sincere gratitude to all the individuals who accompanied us on this route.

This book is dedicated to all people who love the world of micromolecule and do not hesitate to know about it.

Mina Mahmoudi Department of Microbiology Faculty of Medicine Ilam University of Medical Sciences IranSobhan Ghafourian Department of Microbiology Faculty of Medicine Ilam University of Medical Sciences Iran &Behzad Badakhsh

List of Contributors

Maleki Abbas, Clinical Microbiology Research CenterIlam University of Medical SciencesIlamIranBadakhsh Behzad, Department of Internal MedicineIlam University of Medical SciencesIlamIranKazemian Hossein, Department of Microbiology, Faculty of MedicineIlam University of Medical SciencesIlamIranMahmoudi Mina, Department of Microbiology, Faculty of MedicineIlam University of Medical SciencesIlamIranDayjourian (English Editor) Nasrin, Library and Documentation Expert, Information Technology DepartmentHamedan Agricultural and Natural Resources and Education CenterAREEO, HamedanIranSadeghifard Nourkhoda, Department of Microbiology, Faculty of MedicineIlam University of Medical SciencesIlamIranGhafourian Sobhan, Department of Microbiology, Faculty of MedicineIlam University of Medical SciencesIlamIranAhmadi (English Editor) Zahra, Faculty of Literature and Human SciencePayame Noor UniversityIlamIran

An Overview of Pseudomonas aeruginosa

M. Mahmoudi1,S. Ghafourian1,*,B. Badakhsh2
1 Department of Microbiology, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran
2 Department of Gastroenterology, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran

Abstract

Pseudomonas aeruginosa is an absolute aerobic gram-negative bacterium that has attracted the attention of many researchers for many years. There are plenty of reasons to research on P. aeruginosa , which unfortunately has made it an invincible bacterium. Adaptation to environmental changes is one of the most important capabilities that organisms need to survive. This rule also applies to the world of bacteria. P. aeruginosa is one of the most well-known bacteria in terms of adaptation to a variety of biological environments. Besides, P. aeruginosa has a variety of hosts, including humans. It is known as an opportunistic pathogen, therefore infections caused by P. aeruginosa are highly important in immunocompromised patients and it is a major cause of mortality and morbidity in cystic fibrosis patients. Also, P. aeruginosa is the most important cause of nosocomial infections, which can seriously threaten the lives of hospitalized patients. Severe resistance to most antibiotics is one of the other reasons for its success in causing infection and survival. P. aeruginosa can produce many powerful virulent factors that create unique properties in this bacterium. In this chapter, the general characteristics of P. aeruginosa are briefly and usefully explained. So, the reader can get a good idea of this bacterium in a short glance.

Keywords: Overview, Pseudomonas aeruginosa.
*Corresponding author S. Ghafourian: Department of Microbiology, Faculty of Medicine, Ilam University of Medical Sciences, Iran; E-mail: [email protected]

Among all life-threatening bacteria, the name of Pseudomonas aeruginosa(P. aeruginosa) is always shining due to its incredible capacity to stay alive and to destroy its hosts. Initially, it is best to have an overview of the general characteristics of P. aeruginosa to be much more ready for more interesting content of the present book.

P. aeruginosa is a Gram-negative bacterium [1], which is not only obligate aerobe but can also utilize other alternative electron acceptors such as nitrate and can

survive as a facultative anaerobic microorganism at the same time [2, 3]. It is rod-shaped, asprogenous, non-acid-fast and catalase-positive [4].

Besides, P. aeruginosa is a monotrichous flagellated bacterium [5], which makes it different from other fluorescent Pseudomonads (P. putida, P. florescent, etc.) [6], and versatile by one or several polar flagella [7]. Its rod measuring about 0.6 × 2 µm that can be seen as a single bacterium, in pairs and rarely in short chains (pearlescent) [8]. P. aeruginosa appears as multiple colony type that can be considered as different bacteria by non-expert individuals [9]. Generally, two kinds of the colony can be recognized on the agar media. Firstly, it appears as a large and smooth colony with a flat edge and an outstanding center called a fried egg. It is usually isolated from clinical sources. Secondly, it looks rough and outstanding, which is related to natural sources. There is another type, which looks mucous and it is usually isolated from respiratory and urinary secretions [10]. However, the colony of P. aeruginosa has grape-like or tortilla-like odor due to the production of trimethylamine [11, 12]. The optimal temperature for growth is 25°C to 37°C [13]. Also, one of the different features of P. aeruginosa , is its ability to grow at 42°C, which distinguishes it from many other fluorescent Pseudomonas species [14]. The genome size of P. aeruginosa is approximately 5.5–7 Mbp with 65–67% of G+C content [15]. It is also able to use the general source of carbon and nitrogen [16]. P. aeruginosa can use variety of organic molecules, which leads this bacterium to be very ubiquitous [17]. Almost, P. aeruginosa can tolerate hard conditions that's why it is widespread in the environments [18], so, it can be found in soil, water (even distilled water), sewage and specifically in the hospital [19, 20]. In addition, this remarkable property allows P. aeruginosa to be the pathogen for a wide range of hosts including, animals, plants, and humans [21]. In particular, this is an opportunistic and serious pathogen in abnormal host defense, severe burns and cystic fibrosis patients [6, 22, 23]. Indeed, P. aeruginosa is responsible for multiple infections, which can vary from local to systemic as well as the illness severity can be diverse from benign to life-threatening diseases [24].

Many strains of P. aeruginosa produce different kinds of pigments that some of them can dissolve in water and diffuse to the media and some of them are associated with the cell mass. The pigments are prominent to use diagnostic purposes due to its special features. For instance, the pyoverdin is a fluorescent pigment of P. aeruginosa and appears in a yellow-green color that can be seen in a low concentration of iron. In addition, the pyocyanin is the most famous characteristic pigment with the blue-green color. The color of pyocyanin is pH-dependent and it turns red in acidic environments [15]. The pyosyanin is toxic for the ciliated epithelium of the respiratory tract as well as it has a bactericidal effect on Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), Mycobacterium semegmatis [22, 23]. The phenazine-α-carboxylate and chlororaphin can also be seen in orange and green, respectively. The pyorubin can be seen in red color.

Eventually, the pyomelanin is a brown color. There are also some other pigments such as oxychlororaphin etc. [7].

Finally, it may be possible to highlight the importance of P. aeruginosa in a few lines. So, it drives its ability to distribute in the most and hard conditions in nature, having very strong and potent pathogenesis factors and be resistant to most of the antibacterial agents, which makes it one of the most resistant and recalcitrant organisms in the world of creatures.

CONSENT FOR PUBLICATION

Not applicable.

CONFLICT OF INTEREST

The authors declare no conflict of interest, financial or otherwise.

ACKNOWLEDGEMENTS

Declared none.

REFERENCES

[1]Ramalingam B, Parandhaman T, Das SK. Antibacterial effects of biosynthesized silver nanoparticles on surface ultrastructure and nanomechanical properties of gram-negative bacteria viz.Escherichia coli and Pseudomonas aeruginosa. ACS Appl Mater Interfaces 2016; 8(7): 4963-76.[http://dx.doi.org/10.1021/acsami.6b00161] [PMID: 26829373][2]Davies KJ, Lloyd D, Boddy L. The effect of oxygen on denitrification in Paracoccus denitrificans and Pseudomonas aeruginosa. J Gen Microbiol 1989; 135(9): 2445-51.[PMID: 2516869][3]Louie TJ, Bartlett JG, Tally FP, Gorbach SL. Aerobic and anaerobic bacteria in diabetic foot ulcers. Ann Intern Med 1976; 85(4): 461-3.[http://dx.doi.org/10.7326/0003-4819-85-4-461] [PMID: 970773][4]Wu W, Jin Y, Bai F, Jin S. Pseudomonas aeruginosa. Molecular Medical Microbiology 2015753-67.[5]Vaituzis Z, Doetsch RN. Motility tracks: technique for quantitative study of bacterial movement. Appl Microbiol 1969; 17(4): 584-8.[http://dx.doi.org/10.1128/AM.17.4.584-588.1969] [PMID: 4977222][6]Klockgether J, Tümmler B. Recent advances in understanding Pseudomonas aeruginosa as a pathogen. F1000 Res 2017; 6: 1261.[http://dx.doi.org/10.12688/f1000research.10506.1] [PMID: 28794863][7]Brooks G, Carroll K, Butel J, Morse S, Mietzner T. Adelberg Medical Microbiology: Placebo doo 2015.[8]Kirisits MJ, Prost L, Starkey M, Parsek MR. Characterization of colony morphology variants isolated from Pseudomonas aeruginosa biofilms. Appl Environ Microbiol 2005; 71(8): 4809-21.[http://dx.doi.org/10.1128/AEM.71.8.4809-4821.2005] [PMID: 16085879][9]Todar K. Todar's online textbook of bacteriology 2004.[10]Wood CL, Tanner BD, Higgins LA, Dennis JS, Luempert LG, III. Effectiveness of a steam cleaning unit for disinfection in a veterinary hospital. Am J Vet Res 2014; 75(12): 1083-8.[http://dx.doi.org/10.2460/ajvr.75.12.1083] [PMID: 25419808][11]Baron S. Alphaviruses (Togaviridae) and Flaviviruses (Flaviviridae)--Medical Microbiology: University of Texas Medical Branch at Galveston 1996.[12]Ng W. Effect of temperature on growth of Pseudomonas protegens Pf-5 and Pseudomonas aeruginosa PRD-10 in LB Lennox medium. PeerJ Preprints 20182167-9843.[13]Borriello S, Murray P, Funke G. Topley & Wilson’s Microbiology & Microbial infections 2005.[14]Tassios PT, Gennimata V, Maniatis AN, Fock C, Legakis NJ. The Greek Pseudomonas aeruginosa Study GroupEmergence of multidrug resistance in ubiquitous and dominant Pseudomonas aeruginosa serogroup O:11. J Clin Microbiol 1998; 36(4): 897-901.[http://dx.doi.org/10.1128/JCM.36.4.897-901.1998] [PMID: 9542905][15]Dinesh SD, Grundmann H, Pitt TL, Römling U. European-wide distribution of Pseudomonas aeruginosa clone C. Clin Microbiol Infect 2003; 9(12): 1228-33.[http://dx.doi.org/10.1111/j.1469-0691.2003.00793.x] [PMID: 14686989][16]Pirnay JP, Matthijs S, Colak H, et al. Global Pseudomonas aeruginosa biodiversity as reflected in a Belgian river. Environ Microbiol 2005; 7(7): 969-80.[http://dx.doi.org/10.1111/j.1462-2920.2005.00776.x] [PMID: 15946293][17]Favero MS, Carson LA, Bond WW, Petersen NJ. Pseudomonas aeruginosa: growth in distilled water from hospitals. Science 1971; 173(3999): 836-8.[http://dx.doi.org/10.1126/science.173.3999.836] [PMID: 4999114][18]Mashhady MA, Abkhoo J, Jahani S, Abyar S, Khosravani F. Inhibitory Effects of Plant Extracts on Pseudomonas aeruginosa Biofilm Formation. Int J Infect 2016; 3(4): e38199.[http://dx.doi.org/10.17795/iji.38199][19]Lang AB, Horn MP, Imboden MA, Zuercher AW. Prophylaxis and therapy of Pseudomonas aeruginosa infection in cystic fibrosis and immunocompromised patients. Vaccine 2004; 22(Suppl. 1): S44-8.[http://dx.doi.org/10.1016/j.vaccine.2004.08.016] [PMID: 15576201][20]Lyczak JB, Cannon CL, Pier GB. Establishment of Pseudomonas aeruginosa infection: lessons from a versatile opportunist. Microbes Infect 2000; 2(9): 1051-60.[http://dx.doi.org/10.1016/S1286-4579(00)01259-4] [PMID: 10967285][21]Estahbanati HK, Kashani PP, Ghanaatpisheh F. Frequency of Pseudomonas aeruginosa serotypes in burn wound infections and their resistance to antibiotics. Burns 2002; 28(4): 340-8.[http://dx.doi.org/10.1016/S0305-4179(02)00024-4] [PMID: 12052372][22]Gillespie S, Hawkey PM. Principles and practice of clinical bacteriology 2006.[http://dx.doi.org/10.1002/9780470017968][23]Rada B, Leto TL. Pyocyanin effects on respiratory epithelium: relevance in Pseudomonas aeruginosa airway infections. Trends Microbiol 2013; 21(2): 73-81.[http://dx.doi.org/10.1016/j.tim.2012.10.004] [PMID: 23140890][24]Taghinejad J, Hosseinzadeh M, Molayi Kohneshahri S, Javan Jasor V. Pseudomonas aeruginosa: A biological review. Laboratory & Diagnosis 2017; 8(34): 67-82.

History and Etymology

M. Mahmoudi1,S. Ghafourian1,*,N. Sadeghifard1,B. Badakhsh2
1 Department of Microbiology, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran
2 Department of Gastroenterology, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran

Abstract

The greenish-blue color dye on the wounds and bandages of patients was the first characteristic that attracted the attention of researchers in the discovery of this bacterium. Eventually, in 1882, a French pharmacist, Carle Gessard discovered P. aeruginosa from colored cutaneous wounds. He also suggested that this bacterium may be associated with many diseases. Over time, this bacterium found its special niche in the biological and medical sciences due to the complexity, the production of various extracellular products, and the lack of information on how exactly the disease is caused. Along with these findings, several names were assigned to this bacillus bacterium. Finally,Pseudomonas aeruginosa