Cystitis is the presence of bacteria confined to the urinary bladder [2], characterized by dysuria, frequency, urgency, cloudy urine, with or without suprapubic pain [2–5]. It is often associated with pyuria, and occasionally with haematuria [2]. The infection can be classified as either uncomplicated or complicated, where uncomplicated cystitis refers to cases where the host is healthy with no structural or functional abnormalities, and is neither pregnant nor has indwelling devices medical devices such as urinary stents or catheters. All cystitis cases that do not fit these criteria are considered complicated [4]. Approximately 95 % of all urinary tract infections (UTIs) are uncomplicated bladder infections, which will be the focus of this section [6].

Acute, uncomplicated cystitis (AUC) occurs in both men and women, but is primarily present in young, sexually active women, with a frequency of 0.5–0.7 episodes per person annually [3, 4, 7]. Of those infected, approximately 25 % will develop recurrent infections within 6 months, with a significant proportion experiencing a second recurrence within 1 year [4, 8].

Diagnosis is typically based on positive urine cultures in symptomatic individuals. Common pathogens responsible for AUC include uropathogenic Escherichia coli (UPEC), which comprises 80–90 % of the cases, and Staphylococcus saprophyticus, which is responsible for 5–10 % of infections [3, 9]. Occasionally, other Enterobacteriaceae, such as Proteus mirabilis and Klebsiella spp., or Enterococci are isolated [3, 10]. Since treatment of such infections is highly dependent on the mechanisms of action of infective agents, it is important to understand the pathogenesis behind the main culprits of cystitis. Here, we describe the virulence factors utilized by UPEC and S. saprophyticus in the course of a bladder infection.

Pyelonephritis is the inflammation of the upper urinary tract system commonly caused by bacterial infection. Women are more likely than men to develop pyelonephritis due to a shorter urethra. Other factors that predispose people to pyelonephritis are diabetes, kidney stones, bladder tumours, vesicoureteral reflux and other obstructions to the urinary tract that disrupt the normal flow of urine.

Gram-negative bacteria predominate in causing the disease. In particular, E. coli comprise the majority of pyelonephritis-associated bacteria while Klebsiella spp. and Proteus spp. constitute the second and third most common bacteria [17, 18]. Gram-positive bacteria such as Staphylococcus saprophyticus, Enterroccus faecalis, Streptococcus galactiae as well as Mycobacterium tuberculosis are also implicated in rare cases of pyelonephritis but are rarely described in literature [17, 18]. Research in past years has focused on two common ways for bacteria to infect the kidneys and upper urinary tract (UT); the ascending mechanism and the hematogenous mechanism [18]. The ascending mechanism requires the initial migration of uropathogenic bacteria from the opening of the urethra up into the bladder similar to cystitis. The difference is that in pyelonephritis, the bacteria then migrate higher up from the pelvic mucosa into the upper urinary tract primarily by the action of bladder reflux and to some extent flagellar-driven bacterial movement. In addition, obstruction of the normal flow of urine may also contribute to the retention of contaminated urine in the bladder that may propagate into the upper urinary tract and towards the kidneys. In contrast, the hematogenous mechanism is the seeding of circulating bacteria in the blood (bacteremia) as a result of infection at a site distant to the kidneys [18]. Despite the difference in infection pathways, both mechanisms are used by the same set of bacteria, namely E. coli, Klebsiella spp. and Proteus spp. It is important to note however, that most papers describing bacterial virulence mechanisms focus on the more common ascending mechanism.

Urethritis is a urinary tract condition characterized by the inflammation of the urethra. In adults, urethritis is mainly of infectious nature and usually transmitted by sexual contact [31]. In fact, one of the most prevalent types of sexually transmitted infections (STI) in men is nongonococcal urethritis (NGU) [32]. Pathogenic microbes most commonly responsible for NGU include: Chlamydia trachomatis (30–50 % of NGU cases) and Mycoplasma genitalium (10–30 % of NGU cases) [32]. Other pathogens found to be implicated in urethritis include Ureaplasma urealyticum, Haemophilus species, Streptococcus species, Gardnerella vaginalis, herpes simplex viruses, adenoviruses and Trichomonas species [32, 33]. Another form of urethritis is gonococcal urethritis (GU). GU is caused by Neisseria gonorrhoeae [33]. In men, if the bacteria from NGU and GU are allowed to spread, urethritis may lead to epididymo-orchitis (inflammation of the epididymis or testis) and result in impaired fertility [34].

C. trichomatis exists in two morphological forms: the intracellular reticulate body form (RB) and the (extracellular) elementary body form (EB) [35]. The EB form of C. trichomatis is metabolically inactive, but is infectious [36, 37]. It is this form of C. trichomatis that is responsible for the initial colonization of the urethra and in turn the development of NGU. When the EB form of C. trichomatis enters the urethra, they infect susceptible host cells by using a heparin sulfate-like glycosaminoglycan molecule on their cell surface to bind an unknown host cell receptor [37]. Although the receptor is unknown, it is known that these host receptors are localized to the apical surface of polarized cells thus, making the genital epithelium the target of C. trichomatis [36]. Following binding, the EB uses a Type 3 Secretion system to translocate bacterial proteins known as Tarp (translocated actin-recruiting phosphoproteins) into host cells which results in actin recruitment and promotes internalization [36, 38]. When the EBs are endocytosed, they are placed into a membrane bound compartment known as an inclusion and is further transported into the perinuclear location in the infected cell. Following internalization, in approximately 6–8 h, the C. trichomatis EBs differentiate into RBs [37]. RBs are metabolically active and are mainly responsible for C. trichomatis proliferation via binary fission [35, 37]. In 24–72 h, the newly generated C. trichomatis progeny differentiate into EBs and induce cell lysis in order to escape and infect more cells [36, 37]. In response to C. trichomatis infection, the host initiates a proinflammatory Th1 immune response [39] inducing cell mediated immunity resulting in an inflamed urethra. In the case of an extreme Th1 immune response, tissue damage may result [40].