抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Biofilms--matrix-enclosed microbial accretions that adhere to biological or non-biological surfaces--represent a significant and incompletely understood mode of growth for bacteria. Biofilm formation appears early in the fossil record (approximately 3.25 billion years ago) and is common throughout a diverse range of organisms in both the Archaea and Bacteria lineages, including the 'living fossils' in the most deeply dividing branches of the phylogenetic tree. It is evident that biofilm formation is an ancient and integral component of the prokaryotic life cycle, and is a key factor for survival in diverse environments. Recent advances show that biofilms are structurally complex, dynamic systems with attributes of both primordial multicellular organisms and multifaceted ecosystems. Biofilm formation represents a protected mode of growth that allows cells to survive in hostile environments and also disperse to colonize new niches. The implications of these survival and propagative mechanisms in the context of both the natural environment and infectious diseases are discussed in this review.

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Bacterial biofilms: from the natural environment to infectious diseases.

KEGG(Kyoto Encyclopedia of Genes and Genomes)〔和文〕 (特集 ゲノム医学の現在と未来--基礎と臨床) -- (データベース)

Staphylococcus aureus is a major human pathogen that causes a wide range of clinical infections. It is a leading cause of bacteremia and infective endocarditis as well as osteoarticular, skin and soft tissue, pleuropulmonary, and device-related infections. This review comprehensively covers the epidemiology, pathophysiology, clinical manifestations, and management of each of these clinical entities. The past 2 decades have witnessed two clear shifts in the epidemiology of S. aureus infections: first, a growing number of health care-associated infections, particularly seen in infective endocarditis and prosthetic device infections, and second, an epidemic of community-associated skin and soft tissue infections driven by strains with certain virulence factors and resistance to β-lactam antibiotics. In reviewing the literature to support management strategies for these clinical manifestations, we also highlight the paucity of high-quality evidence for many key clinical questions.

Staphylococcus aureus Infections: Epidemiology, Pathophysiology, Clinical Manifestations, and Management

https://hal.archives-ouvertes.fr/hal-00567285/document

Antibiotic resistance of bacterial biofilms

Increasing attention has been focused on understanding bacterial biofilms and this growth modality's relation to human disease. In this review we explore the genetic regulation and molecular components involved in biofilm formation and maturation in the context of the Gram-positive cocci, Staphylococcus aureus. In addition, we discuss diseases and host immune responses, along with current therapies associated with S. aureus biofilm infections and prevention strategies.

https://www.tandfonline.com/doi/pdf/10.4161/viru.2.5.17724

Staphylococcus aureus biofilms: properties, regulation, and roles in human disease.

Unequivocal direct observations have established that the bacteria that cause device-related and other chronic infections grow in matrix-enclosed biofilms. The diagnostic and therapeutic strategies that have served us so well in the partial eradication of acute epidemic bacterial diseases have not yielded accurate data or favorable outcomes when applied to these biofilm diseases. We discuss the potential benefits of the application of the new methods and concepts developed by biofilm science and engineering to the clinical management of infectious diseases.

/pdf/the-application-of-biofilm-science-to-the-study-and-control-2mzajvvm9u.pdf

The application of biofilm science to the study and control of chronic bacterial infections

Catheter-associated urinary tract infections (CAUTIs) represent the most common type of nosocomial infection and are a major health concern due to the complications and frequent recurrence. These infections are often caused by Escherichia coli and Proteus mirabilis. Gram-negative bacterial species that cause CAUTIs express a number of virulence factors associated with adhesion, motility, biofilm formation, immunoavoidance, and nutrient acquisition as well as factors that cause damage to the host. These infections can be reduced by limiting catheter usage and ensuring that health care professionals correctly use closed-system Foley catheters. A number of novel approaches such as condom and suprapubic catheters, intermittent catheterization, new surfaces, catheters with antimicrobial agents, and probiotics have thus far met with limited success. While the diagnosis of symptomatic versus asymptomatic CAUTIs may be a contentious issue, it is generally agreed that once a catheterized patient is believed to have a symptomatic urinary tract infection, the catheter is removed if possible due to the high rate of relapse. Research focusing on the pathogenesis of CAUTIs will lead to a better understanding of the disease process and will subsequently lead to the development of new diagnosis, prevention, and treatment options.

/pdf/complicated-catheter-associated-urinary-tract-infections-due-4k0xw7kb6h.pdf

Complicated Catheter-Associated Urinary Tract Infections Due to Escherichia coli and Proteus mirabilis

Summary: Microorganisms coexist in a complex milieu of bacteria, fungi, archaea, and viruses on or within the human body, often as multifaceted polymicrobial biofilm communities at mucosal sites and on abiotic surfaces. Only recently have we begun to appreciate the complicated biofilm phenotype during infection; moreover, even less is known about the interactions that occur between microorganisms during polymicrobial growth and their implications in human disease. Therefore, this review focuses on polymicrobial biofilm-mediated infections and examines the contribution of bacterial-bacterial, bacterial-fungal, and bacterial-viral interactions during human infection and potential strategies for protection against such diseases.

Polymicrobial Interactions: Impact on Pathogenesis and Human Disease

Acute septic arthritis may develop as a result of hematogenous seeding, direct introduction, or extension from a contiguous focus of infection. The pathogenesis of acute septic arthritis is multifactorial and depends on the interaction of the host immune response and the adherence factors, toxins, and immunoavoidance strategies of the invading pathogen. Neisseria gonorrhoeae and Staphylococcus aureus are used in discussing the host-pathogen interaction in the pathogenesis of acute septic arthritis. While diagnosis rests on isolation of the bacterial species from synovial fluid samples, patient history, clinical presentation, laboratory findings, and imaging studies are also important. Acute nongonococcal septic arthritis is a medical emergency that can lead to significant morbidity and mortality. Therefore, prompt recognition, rapid and aggressive antimicrobial therapy, and surgical treatment are critical to ensuring a good prognosis. Even with prompt diagnosis and treatment, high mortality and morbidity rates still occur. In contrast, gonococcal arthritis is often successfully treated with antimicrobial therapy alone and demonstrates a very low rate of complications and an excellent prognosis for full return of normal joint function. In the case of prosthetic joint infections, the hardware must be eventually removed by a two-stage revision in order to cure the infection.

Mark E. Shirtliff

Papers

Staphylococcus aureus biofilms: properties, regulation, and roles in human disease.

The application of biofilm science to the study and control of chronic bacterial infections

Complicated Catheter-Associated Urinary Tract Infections Due to Escherichia coli and Proteus mirabilis

Polymicrobial Interactions: Impact on Pathogenesis and Human Disease

Acute Septic Arthritis