Ancient dental pulp: Masterpiece tissue for paleomicrobiology.

INTRODUCTION: Dental pulp with special structure has become a good reference sample in paleomicrobiology-related blood-borne diseases, many pathogens were detected by different methods based on the diagnosis of nucleic acids and proteins. OBJECTIVES: This review aims to propose the preparation process from ancient teeth collection to organic molecule extraction of dental pulp and summary, analyze the methods that have been applied to detect septicemic pathogens through ancient dental pulps during the past 20 years following the first detection of an ancient microbe. METHODS: The papers used in this review with two main objectives were obtained from PubMed and Google scholar with combining keywords: "ancient," "dental pulp," "teeth," "anatomy," "structure," "collection," "preservation," "selection," "photography," "radiography," "contamination," "decontamination," "DNA," "protein," "extraction," "bone," "paleomicrobiology," "bacteria," "virus," "pathogen," "molecular biology," "proteomics," "PCR," "MALDI-TOF," "LC/MS," "ELISA," "immunology," "immunochromatography," "genome," "microbiome," "metagenomics." RESULTS: The analysis of ancient dental pulp should have a careful preparation process with many different steps to give highly accurate results, each step complies with the rules in archaeology and paleomicrobiology. After the collection of organic molecules from dental pulp, they were investigated for pathogen identification based on the analysis of DNA and protein. Actually, DNA approach takes a principal role in diagnosis while the protein approach is more and more used. A total of seven techniques was used and ten bacteria (Yersinia pestis, Bartonella quintana, Salmonella enterica serovar Typhi, Salmonella enterica serovar Paratyphi C, Mycobacterium leprae, Mycobacterium tuberculosis, Rickettsia prowazeki, Staphylococcus aureus, Borrelia recurrentis, Bartonella henselae) and one virus (Anelloviridae) were identified. Y. pestis had the most published in quantity and all methods were investigated for this pathogen, S. aureus and B. recurrentis were identified by three different methods and others only by one. The combining methods interestingly increase the positive rate with ELISA, PCR and iPCR in Yersinia pestis diagnosis. Twenty-seven ancient genomes of Y. pestis and one ancient genome of B. recurrentis were reconstructed. Comparing to the ancient bone, ancient teeth showed more advantage in septicemic diagnosis. Beside pathogen identification, ancient pulp help to distinguish species. CONCLUSIONS: Dental pulp with specific tissue is a suitable sample for detection of the blood infection in the past through DNA and protein identification with the correct preparation process, furthermore, it helps to more understand the pathogens of historic diseases and epidemics.

The potential role of interleukin-37 in infectious diseases.

Interleukin-37 (IL-37) is a newly introduced cytokine to interleukin-1 family. Many studies have demonstrated that IL-37 owns immunosuppressive effects against both innate and acquired immune responses via inhibition of several inflammatory mediators. Thence, IL-37 has anti-inflammatory action in some diseases including cancer, autoimmune diseases, cardiovascular diseases and infectious diseases. Recent investigations have reported the important role of IL-37 in immunity against viral, bacterial and fungal infections as they prevent inappropriate immune activation and suppress the inflammation induced by these infectious agents. Thus, IL-37 could play a crucial role in protecting host tissues from injury during infections by damping excessive inflammatory reactions. However, the precise roles of IL-37 in infectious diseases remain largely unknown. The current review shed light on the pivotal role of IL-37 in infectious diseases such as the human immunodeficiency virus-1 (HIV-1), viral myocarditis, hepatitis C virus (HCV), hepatitis B virus (HBV), tuberculosis, leprosy, pneumococcal pneumonia, listeria infection, aspergillosis, candidiasis and eumycetoma. In conclusion, this review reported that IL-37 has a crucial role in reducing infection-associated inflammation and has a good impact on inflammation-induced pathology. However, tight regulation that achieved balance between effector immune responses that required for pathogen elimination and limited tissue damage that resulted from excessive inflammation should be existed in the potential IL-37 therapy to prevent clinical complications of a disease.

Protein Tagging, Destruction and Infection.

Cells possess protein quality control mechanisms to maintain proper cellular homeostasis. In eukaryotes, the roles of the ubiquitination and proteasome-mediated degradation of cellular proteins is well established. Recent studies have elucidated protein tagging mechanisms in prokaryotes, involving transfer messenger RNA (tmRNA) and pupylation. In this review, newer insights and bioinformatics analysis of two distinct bacterial protein tagging machineries are discussed. The machinery for tmRNAmediated tagging is present in several eubacterial representatives, e.g. Escherichia coli, Mycobacterium tuberculosis, Bacillus subtilis etc., but not in two archaeal representatives, such as Thermoplasma acidophilum and Sulfolobus solfataricus. On the other hand, the machinery involving tagging with the prokaryotic ubiquitin-like protein (Pup) is absent in most bacteria but is encoded in some eubacterial representatives, e.g. Mycobacterium tuberculosis and Mycobacterium leprae. Furthermore, molecular details on the relationship between protein tagging and enzymes involved in protein degradation in bacteria during infection are emerging. Several pathogenic bacteria that do not express the major ATP-dependent proteases, Lon and Caseinolytic protease (ClpP), are avirulent. Also, some ATP-independent peptidases, such as PepA and PepN, modulate the infection process. The roles of bacterial proteins involved in tagging and degradation during infection are discussed. These aspects add a new dimension to better understanding of the peculiarities of host-pathogen interactions.

The immunology and inflammatory responses of human melanocytes in infectious diseases.

Melanin is a canonical and major defense molecule in invertebrates but its role in mammalian immunity remains unexplored. In contrast, several recent studies have highlighted the emerging innate immune activities of human melanin-producing cells which can sense and respond to bacterial and viral infections. Indeed, the skin is a major portal of entry for pathogens such as arboviruses (Chikungunya, Dengue) and bacteria (mycobacterium leprae, Leptospira spirochetes). Melanocytes of the epidermis could contribute to the phagocytosis of these invading pathogens and to present antigens to competent immune cells. Melanocytes are known to produce key cytokines such as IL-1ß, IL6 and TNF-α as well as chemokines. These molecules will subsequently alert macrophages, neutrophils, fibroblasts and keratinocytes through unique crosstalk mechanisms. The infection and the inflammatory responses will control melanocyte's immune and metabolic functions and could contribute to skin manifestations (rash, hyper or de-pigmentation, epidermolysis and psoriasis-like lesions). This review will address the potential role of melanocytes in immunity, inflammation and infection of the skin in health and diseases.

Vasculitis and infectious diseases.

Vasculitis usually presents without a well-known underline cause (idiopathic vasculitis), nevertheless, it is sometimes possible to find out one or more causative agents (secondary vasculitis). Nowadays, thanks to the increasing amount of precise diagnostic tools, a piece of idiopathic vasculitis is reclassified as associated with probable etiology, which can be set off by several factors, such as infections. Infections are considered to be the most common cause of secondary vasculitis. Virtually, every infectious agent can trigger a vasculitis by different mechanisms which can be divided in two main categories: direct and indirect. In the former, infectious agents destroy directly the vascular wall leading, eventually, to a subsequent inflammatory response. In the latter, indirect form, they stimulate an immune response against blood vessels. Different infectious agents are able to directly damage the vascular wall. Among these, it is possible to recognize Staphylococcus spp, Streptococcus spp, Salmonella spp, Treponema spp, Rickettsia spp, Cytomegalovirus, Herpes Simplex Virus 1 and 2, and many others which have a peculiar tropism for endothelial cells. Conversely, another group of microbial agents, such as Mycobacterium tuberculosis, Mycobacterium leprae, Hepatits B Virus, Human Immunodeficiency Virus and others, trigger vasculitis in the indirect way. This is due to the fact that they can share epitopes with the host or modify self-antigens, thus leading to a cross-self reaction of the immune system. These mechanism, in turn, leads to immunological responses classified as type I-IV by Gell-Coombs. Nevertheless, it is difficult to strictly separate the direct and indirect forms, because most infectious agents can cause vasculitis in both ways (mixed forms). This paper will analyze the link between infectious agents and vasculitis, focusing on direct and indirect secondary vasculitis, and on a group of probable infection-related idiopathic vasculitis, and finally on a group of idiopathic vasculitis with microbiological triggers. Furthermore, a diagnostic and therapeutic approach to vasculitis when an underline infection has been suspected is suggested.

Current and past strategies for bacterial culture in clinical microbiology.

A pure bacterial culture remains essential for the study of its virulence, its antibiotic susceptibility, and its genome sequence in order to facilitate the understanding and treatment of caused diseases. The first culture conditions empirically varied incubation time, nutrients, atmosphere, and temperature; culture was then gradually abandoned in favor of molecular methods. The rebirth of culture in clinical microbiology was prompted by microbiologists specializing in intracellular bacteria. The shell vial procedure allowed the culture of new species of Rickettsia. The design of axenic media for growing fastidious bacteria such as Tropheryma whipplei and Coxiella burnetii and the ability of amoebal coculture to discover new bacteria constituted major advances. Strong efforts associating optimized culture media, detection methods, and a microaerophilic atmosphere allowed a dramatic decrease of the time of Mycobacterium tuberculosis culture. The use of a new versatile medium allowed an extension of the repertoire of archaea. Finally, to optimize the culture of anaerobes in routine bacteriology laboratories, the addition of antioxidants in culture media under an aerobic atmosphere allowed the growth of strictly anaerobic species. Nevertheless, among usual bacterial pathogens, the development of axenic media for the culture of Treponema pallidum or Mycobacterium leprae remains an important challenge that the patience and innovations of cultivators will enable them to overcome.

Urticaria and bacterial infections.

The association between urticaria and infectious diseases has been discussed for >100 years. However, a causal relationship with underlying or precipitating infection is difficult to establish. The purpose of this work was to perform a systematic analysis of the published cases of urticaria associated with bacterial infections. We give an umbrella breakdown of up-to-date systematic reviews and other important publications on the complex association of urticaria and bacterial infections. We did a Medline search, for English language articles published until January 2014, using the key words "urticaria" and "bacteria/bacterial disease"; a second analysis was performed in groups of bacteria and using each germ name as a key word. Many bacterial infections have been associated with urticaria manifestation, such as Helicobacter pylori, Streptococcus, Staphylococcus, Mycoplasma pneumonia, Salmonella, Brucella, Mycobacterium leprae, Borrelia, Chlamydia pneumonia, and Yersinia enterocolitica. In some cases the skin manifestations, described as urticaria, could be caused by the presence of the microorganism in the skin, or for the action of their toxins, or to the complement activation mediated by circulating immune complexes. Although only a weak association with urticaria of unclear pathogenesis exists, clinicians should consider these bacterial agents in the workup of the patients with urticaria. The eradication of the infection could, in fact, lead to the resolution of urticaria. Prospective studies and well-structured research are obviously needed to better clarify the real role of bacteria in the pathogenesis of urticaria and their relative prevalence.

Palaeopathology and genes: investigating the genetics of infectious diseases in excavated human skeletal remains and mummies from past populations.

The aim of this paper is to review the use of genetics in palaeomicrobiology, and to highlight the importance of understanding past diseases. Palaeomicrobiology is the study of disease pathogens in skeletal and mummified remains from archaeological contexts. It has revolutionarised our understanding of health in the past by enabling a deeper knowledge of the origins and evolution of many diseases that have shaped us as a species. Bacterial diseases explored include tuberculosis, leprosy, bubonic plague, typhoid, syphilis, endemic and epidemic typhus, trench fever, and Helicobacter pylori. Viral diseases discussed include influenza, hepatitis B, human papilloma virus (HPV), human T-cell lymphotrophic virus (HTLV-1) and human immunodeficiency virus (HIV). Parasitic diseases investigated include malaria, leishmaniasis, Chagas' disease, roundworm, whipworm, pinworm, Chinese liver fluke, fleas and lice. Through a better understanding of disease origins and their evolution, we can place into context how many infectious diseases are changing over time, and so help us estimate how they may change in the future.

The pattern of bacterial isolates and drug sensitivities of infected ulcers in patients with leprosy in ALERT, Kuyera and Gambo hospitals, Ethiopia.

INTRODUCTION: Leprosy remains a public health problem, mainly in Africa, Asia and Latin America. Leprosy has many complications that include leprosy reactions, development of plantar and hand ulcerations, lagophthalomus and corneal anesthesia. OBJECTIVES: In Ethiopia there is scarce information on the pattern of bacterial isolates and drug sensitivities of infected ulcers in patients with leprosy. This study was undertaken to identify the bacteriology of infected ulcers and to determine their antimicrobial susceptibility pattern. STUDY DESIGN: A descriptive cross-sectional study was conducted in 245 informed and consented leprosy patients with infected ulcers visiting ALERT, Kuyera and Gambo hospitals during the period August 2006 to May 2007. MATERIAL AND METHODS: Wound aspirate specimens were collected from ulcers of each patient aseptically and inoculated into standard bacteriological media. Antimicrobial susceptibility testing was performed for all isolates according to the criteria of the National Committee for Clinical Laboratory Standards (NCCLS) by disk diffusion method. RESULTS: Of the 245 patients investigated, 64.1% were males and 35.9% females (P < 0.05). The average age of the patients was 50 years (age range 13 to 92 years). According to Ridley-Jopling classifications, patients presented with TT (3.7%), BT, (31.4%), BL (44.5%) and LL (15.9%) types of leprosy. Plantar and hand ulcers were observed in 92.2% and 7.8% of patients, respectively. According the patients, the commonest cause of their ulcers was 'spontaneous' (56.7%). There were 44% Gram-positive and 56% Gram negative bacteria (P > 0.05). Proteus spp. accounted for 29.5% of the total isolates followed by Staphylococcus spp. (28.8%), beta-hemolytic streptococci (15.1%) and different types of Gram-negative bacteria (26.2%). Multiple organisms (two or three) were isolated from 19.6% patients. Of the 212 wound samples cultured anaerobically, 5.2% were positive for anaerobic culture. In this study both Gram-positive and Gram negative bacteria showed decreased sensitivity to most antimicrobial agents tested. CONCLUSION: Proteus spp. was the most common isolate from infected ulcers. Ciprofloxacin, norfloxacin and gentamicin were the most effective drugs against the tested bacteria mainly for Gram-negative bacteria. This refers to the in vitro-sensitivity during the study period. The results of this study may help inform clinicians about the selection of an antibiotic in situations where use of an antibiotic may be indicated.

Clinicopathological features and the practice of diagnosing infectious cutaneous granulomas in Egypt.

OBJECTIVE: To present the clinicopathological features and the practice of diagnosing infectious cutaneous granulomas in Egypt. METHODS: This study included all cases diagnosed with infectious cutaneous granuloma during the period 2004-2010 at Al-Hussein University Hospital, Cairo. Clinical and histological features were recorded, along with the positivity rate (PR) for each diagnostic method. RESULTS: This study included 233 cases (150 males and 83 females) with a mean age of 47 years. Three groups of infection were recorded: bacterial infections (73.8% Mycobacterium and 3.9% non-Mycobacterium), parasitic infestations (16.7%), and deep fungal infections (5.6%). Tuberculosis cases formed the largest granuloma group (40.8%), followed by leprosy (31.7%) and leishmaniasis (15.9%). A total of 36 cases were diagnosed by direct smear (PR 15.5%), 61 cases by skin biopsy (PR 31.0%), 84 cases by intradermal test (PR 63.6%), 26 cases by serological tests (PR 60.5%), 18 cases by tissue culture (PR 69.2%), and eight cases by PCR (PR 100%). CONCLUSIONS: Mycobacterial infections constitute the most common infectious cutaneous granulomas among Egyptians. Routine methods such as direct smear, skin biopsy, and intradermal tests remain the most commonly applied and economical methods for diagnosis in developing countries, although specific methods such as tissue culture and PCR have higher positivity rates in the diagnosis.

Resistance to rifampicin: at the crossroads between ecological, genomic and medical concerns.

The first antibiotic of the ansamycin family, rifampicin (RIF), was isolated in 1959 and was introduced into therapy in 1962; it is still a first-line agent in the treatment of diseases such as tuberculosis, leprosy and various biofilm-related infections. The antimicrobial activity of RIF is due to its inhibition of bacterial RNA polymerase (RNAP). Most frequently, bacteria become resistant to RIF through mutation of the target; however, this mechanism is not unique. Other mechanisms of resistance have been reported, such as duplication of the target, action of RNAP-binding proteins, modification of RIF and modification of cell permeability. We suggest that several of these alternative resistance strategies could reflect the ecological function of RIF, such as autoregulation and/or signalling to surrounding microorganisms. Very often, resistance mechanisms found in the clinic have an environmental origin. One may ask whether the introduction of the RIF analogues rifaximin, rifalazil, rifapentine and rifabutin in the therapeutic arsenal, together with the diversification of the pathologies treated by these molecules, will diversify the resistance mechanisms of human pathogens against ansamycins.

Was there a Bacteriological Revolution in late nineteenth-century medicine?

That there was a 'Bacteriological Revolution' in medicine in the late nineteenth-century, associated with the development of germ theories of disease, is widely assumed by historians; however, the notion has not been defined, discussed or defended. In this article a characterisation is offered in terms of four linked rapid and radical changes: (i) a series of discoveries of the specific causal agents of infectious diseases and the introduction of Koch's Postulates; (ii) a reductionist and contagionist turn in medical knowledge and practice; (iii) greater authority for experimental laboratory methods in medicine; (iv) the introduction and success of immunological products. These features are then tested against developments in four important but previously neglected diseases: syphilis, leprosy, gonorrhoea and rabies. From these case-studies I conclude that the case for a Bacteriological Revolution in late nineteenth-century medicine in Britain remains unproven. I suggest that historians have read into the 1880s changes that occurred over a much longer period, and that while there were significant shifts in ideas and practices over the decade, the balance of continuities and changes was quite uneven across medicine. My argument is only for Britain; in other countries the rate and extent of change may have been different.

Interleukin-18 (IL-18) and infectious diseases, with special emphasis on diseases induced by intracellular pathogens.

Interleukin-18 (IL-18) is a novel cytokine mainly produced by activated macrophages. IL-18 was originally called interferon-gamma inducing factor, due to its action in inducing IFN-gamma secretion from Th1 cells, NK cells and NKT cells. It has been reported that IL-18 may play important roles in various diseases including cancer and infectious diseases. This review deals with the roles of IL-18 in infectious diseases, with special emphasis on IL-18 in infectious diseases caused by intracellular pathogens including Mycobacterium tuberculosis, Mycobacterium leprae, Listeria monocytogenes and Salmonella typhimurium.

Bacteriological study of pus isolates from neuropathic plantar ulcers associated with acute inflammatory phase.

In this retrospective study, sensitivity of organisms cultured from ulcers of leprosy patients without and with diabetes mellitus, diabetic patients without leprosy and patients with ulcers from other causes was examined. The profile of organisms grown from these groups of patients did not differ significantly. However, there was a high prevalence of organisms like Proteus, E. coli and Enterococcus in the ulcers of leprosy patients indicating faecal contamination of the ulcers. Co-trimaxazole and tetracycline were of little value in the treatment of these ulcers. We therefore recommend that in situations where there is no culture facility, the patients be started on a course of penicillin and gentamycin. If these antibiotics fail, it would be necessary to use more advanced antibiotics like norfloxacin, amikacin and ciprofloxacin.

[Infections with cutaneous and nervous system alterations]. / Infecciones con afectación cutánea y del sistema nervioso.

OBJECTIVE: We review and update the clinical and diagnostic aspects in the most representative neurocutaneous infections, emphasizing the features of interdisciplinary interest. METHODS: Human skin is the primary host barrier against infection and his importance is critical in the immunocompromised population. The genetic hability of pathogen micro-organisms to bind the adhesion molecules of cellular membranes defines the anatomic affinity of each species. Cutaneous involvement can be crucial for diagnosis in infectious diseases. The characteristics of the elemental lesions and the accessible cytology, bacteriology and histopathology procedures, usually leads to a specific diagnosis. We highlight the cutaneous manifestations of the acute and subacute bacterial meningitides. We review the clinico-pathologic characteristics of the meningoencephalitidis associated to the viral exanthems. We describe the chronic bacterial entities with prominent cutaneous and neural affectation as lepra, syphilis and borreliosis, as well as the numerous clinical forms of presentation of herpesvirus hominis and varicellazoster. Finally, we stand out the transcendency of cutaneous findings in the HIV set. CONCLUSIONS: The appropriate interpretation of the infectious cutaneous semiology, supplemented with exams of direct samples, allow frequently to reach an ethiologic or orientated diagnosis, in a rapid, economic and non-invasive way. This information must be carefully incorporated to the study of high-morbidity infections, as there that concerns to the nervous system.

Immunity to intracellular bacteria.

Immunity to intracellular bacteria including Mycobacterium tuberculosis, Mycobacterium leprae, and Listeria monocytogenes depends on specific T cells. Evidence to be described suggests that CD4 alpha/beta T cells, CD8 alpha/beta T cells and gamma/delta T cells which interact with each other and with macrophages contribute to acquired resistance against as well as pathogenesis of intracellular bacterial infections.

Non-sporing anaerobes in hospital sepsis.

In comparison to normal controls, the non-sporing anaerobes were often isolated from orodental sepsis (42% to 44.4%), chronic suppurative otitis media (40%), septic abortion (40.3%), uterocervical wound (45.4%), vaginitis (50%) and cancer cervix (50%). This was true (40%) in perforating ulcers of foot in leprosy. These organisms were less frequently noted in abdominal (11%) and episiotomy (22.8%) wounds and leucorrhoea (33.3%). The role of non-sporing anaerobes was also suggested by the high percentage ratio of number of isolates to number of cases and by its primary isolation in moderate to heavy number. Barring the cases of cancer cervix, the aerobic bacteria were the most common (78.8% to 100%) in all other conditions.

Bacteriology of infected hands and feet in leprosy patients.

70 cases of infected hands and feet admitted to ALERT Hospital during 1986/1987 (3/10/86-5/5/87) were studied for the infecting organisms and the sensitivity of these organisms to available antibiotics. Single organisms were isolated in 56 cases (95%), two organisms were isolated in 3 cases (5%), no organisms were isolated in 11 cases (15.7%). Proteus was the commonest organism. Most effective drug was Ampicillin. Three organisms isolated in 7 cases proved resistant to all drugs tested. The study shows that commonly available drugs are effective in the great majority of secondary infections in leprosy patients.